The droplets' phospholipid membranes proved no barrier to the passage of dioxins, which accumulated satisfactorily in the oil.
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And each droplet is surrounded by a membrane composed of a substance called a phospholipid which, unlike oil, is attractive to water.
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"Precise tuning of the laser parameters allowed us to induce a process called hemifusion at the contact point of two phospholipid membranes," they write.
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In enzymology, a methylene-fatty-acyl-phospholipid synthase () is an enzyme that catalyzes the chemical reaction :S-adenosyl-L-methionine + phospholipid olefinic fatty acid \rightleftharpoons S-adenosyl-L-homocysteine + phospholipid methylene fatty acid Thus, the two substrates of this enzyme are S-adenosyl methionine and phospholipid olefinic fatty acid, whereas its two products are S-adenosylhomocysteine and phospholipid methylene fatty acid. This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases. The systematic name of this enzyme class is S-adenosyl-L-methionine:unsaturated-phospholipid methyltransferase (methenylating). This enzyme is also called unsaturated- phospholipid methyltransferase.
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Phospholipid vesicles have also been studied in biochemistry. For such studies, a homogeneous phospholipid vesicle suspension can be prepared by extrusion or sonication, injection of a phospholipid solution into the aqueous buffer solution membranes. In this way aqueous vesicle solutions can be prepared of different phospholipid composition, as well as different sizes of vesicles.
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In enzymology, a phospholipid-translocating ATPase () is an enzyme that catalyzes the chemical reaction :ATP + H2O + phospholipid in \rightleftharpoons ADP + phosphate + phospholipid out The 3 substrates of this enzyme are ATP, H2O, and phospholipid, whereas its 3 products are ADP, phosphate, and phospholipid. This enzyme belongs to the family of hydrolases, specifically those acting on acid anhydrides to catalyse transmembrane movement of substances. The systematic name of this enzyme class is ATP phosphohydrolase (phospholipid-flipping). Other names in common use include Mg2+-ATPase, flippase, and aminophospholipid-transporting ATPase.
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In enzymology, a cyclopropane-fatty-acyl-phospholipid synthase () is an enzyme that catalyzes the chemical reaction :S-adenosyl-L-methionine + phospholipid olefinic fatty acid \rightleftharpoons S-adenosyl-L-homocysteine + phospholipid cyclopropane fatty acid Thus, the two substrates of this enzyme are S-adenosyl methionine and phospholipid olefinic fatty acid, whereas its two products are S-adenosylhomocysteine and phospholipid cyclopropane fatty acid. This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases. The systematic name of this enzyme class is S-adenosyl-L-methionine:unsaturated-phospholipid methyltransferase (cyclizing). Other names in common use include cyclopropane synthetase, unsaturated-phospholipid methyltransferase, cyclopropane synthase, cyclopropane fatty acid synthase, cyclopropane fatty acid synthetase, and CFA synthase.
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Phospholipid scramblase 4, also known as Ca2+-dependent phospholipid scramblase 4, is a protein that is encoded in humans by the PLSCR4 gene.
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Phospholipid scramblase 2, also known as Ca2+-dependent phospholipid scramblase 2, is a protein that in humans is encoded by the PLSCR2 gene.
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The protein-phospholipid complex associates with a lipid bilayer, discharges the bound phospholipid into the bilayer, and upon recognition of another membrane bound phospholipid, extracts the phospholipid and disassociates with the lipid bilayer. Additionally, the PtdIns and PtdCho affinity of Sec14p has been suggested to act as a localizing force, bringing Sec14p into proximity to the ER or Golgi body where it may aid in the formation of transport vesicles.
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Used surfactant phospholipid materials are taken up into epithelial type II cells by pulmonary macrophages. Another important protein that contributes to outcome of surfactant metabolism dysfunction is ABCA3, a transmembrane phospholipid transporter in lamellar body. ABCA3 has two ATP binding sites in the cytoplasmic domain to power phospholipid transportation through ATP hydrolysis. ABCA3 is synthesized in endoplasmic reticulum and transported through Golgi apparatus to the membrane of lamellar body.
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Poster on EthosomesEthosomes are phospholipid nanovesicles used for dermal and transdermal delivery of molecules.
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Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule.
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Moreover, Vps26 does not have similar sequences as arrestins for GPCR and phospholipid interactions.
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In the maturation of the red blood cell lineage (see erythropoiesis) from mitochondria-bearing reticulocytes to mature mitochondria-free erythrocytes in rabbits, the mitochondria accumulate phospholipid-bound 13(S)-HODE in their membranes due to the action of a lipoxygenase which (in rabbits, mice, and other sub-primate vertebrates) directly metabolizes linoleic acid-bound phospholipid to 13(S)-HpODE-bound phospholipid which is rapidly reduced to 13(S)-HODE-bound phospholipid. It is suggested that the accumulation of phospholipid-bound 13(S)-HpODE and/or 13(S)-HODE is a critical step in rendering mitochondria more permeable thereby triggering their degradation and thence maturation to erythrocytes. However, functional inactivation of the phospholipid-attacking lipoxygenase gene in mice does not cause major defects in erythropoiesis. It is suggested that mitochondrial degradation proceeds through at least two redundant pathways besides that triggered by lipoxygenase-dependent formation of 13(S)-HpODE- and 13(S)-HODE-bound phospholipids viz.
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POPC is a phosphatidylcholine. It is a diacylglycerol and phospholipid. The full name is 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. It is an important phospholipid for biophysical experiments and has been used to study various subjects such as lipid rafts.
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Phospholipid scramblase 1 is an enzyme that in humans is encoded by the PLSCR1 gene.
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Phospholipase A1 cleaves phospholipid at the SN1 position forming a lysophospholipid and a fatty acid.
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Phospholipid transfer protein is a protein that in humans is encoded by the PLTP gene.
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Due to the selective permeability of the phospholipid membrane, only specific compounds can pass through it.
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Diagram of liposome showing a phospholipid bilayer surrounding an aqueous interior. One type of nanoparticle involves use of liposomes as drug molecule carriers. The diagram on the right shows a standard liposome. It has a phospholipid bilayer separating the interior from the exterior of the cell.
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Phospholipid scramblase family member 5 is a protein that in humans is encoded by the PLSCR5 gene.
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It is synthesized by head group exchange of a phosphatidylcholine enriched phospholipid using the enzyme phospholipase D.
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Probable phospholipid-transporting ATPase IF is an enzyme that in humans is encoded by the ATP11B gene.
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ATPase phospholipid transporting 9A (putative) is a protein that in humans is encoded by the ATP9A gene.
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SignaFresh is a brand of a natural phospholipid based on lysophosphatidylethanolamine (LPE), a biopesticide approved by US EPA.
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Calcium also binds to the phospholipid layer of the cell membrane, anchoring proteins associated with the cell surface.
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In enzymology, a platelet-activating factor acetyltransferase () is an enzyme that catalyzes the chemical reaction :1-alkyl-2-acetyl-sn- glycero-3-phosphocholine + 1-organyl-2-lyso-sn-glycero-3-phospholipid \rightleftharpoons 1-organyl-2-lyso-sn-glycero-3-phosphocholine + 1-alkyl-2-acetyl-sn-glycero-3-phospholipid Thus, the two substrates of this enzyme are 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine and 1-organyl-2-lyso- sn-glycero-3-phospholipid, whereas its two products are 1-organyl-2-lyso-sn- glycero-3-phosphocholine and 1-alkyl-2-acetyl-sn-glycero-3-phospholipid. This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is 1-alkyl-2-acyl-sn- glycero-3-phosphocholine:1-organyl-2-lyso-sn-glyce ro-3-phospholipid acetyltransferase. This enzyme is also called PAF acetyltransferase.
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KCT is similar to the activated partial thromboplastin time test, except it does not use exogenous phospholipid. Thus, a confirmatory test that uses excess phospholipid is needed to validate the presence of lupus anticoagulants. Otherwise diluting the test plasma in normal plasma before testing provides characteristic mixing patterns.Exner,T (1978).
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It is known that protein aggregates in vitro can destabilize artificial phospholipid bilayers, leading to permeabilization of the membrane.
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They are responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell's membrane (transverse diffusion, also known as a "flip-flop" transition). The possibility of active maintenance of an asymmetric distribution of molecules in the phospholipid bilayer was predicted in the early 1970s by Mark Bretscher. Although phospholipids diffuse rapidly in the plane of the membrane, their polar head groups cannot pass easily through the hydrophobic center of the bilayer, limiting their diffusion in this dimension. Some flippases - often instead called scramblases \- are energy-independent and bidirectional, causing reversible equilibration of phospholipid between the two sides of the membrane, whereas others are energy- dependent and unidirectional, using energy from ATP hydrolysis to pump the phospholipid in a preferred direction.
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It has been proposed to be conjugated from arachidonoyl-CoA or arachidonoyl phospholipids and dopamine, but in vitro experiments do not support this theory. However, the indirect biosynthesis of phospholipid esters with dopamine may be possible, as dopamine can induce the aminolysis of the glycerol-fatty acid bonds in phospholipid chains (arachidonoyl, palmitoyl, linoleyl, etc.).
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Starting with a technique commonly used to deposit molecules on a solid surface, Langmuir–Blodgett deposition, scientists are able to assemble phospholipid membranes of arbitrary complexity layer by layer. These artificial phospholipid membranes support functional insertion both of purified and of in situ expressed membrane proteins. The technique could help astrobiologists understand how the first living cells originated.
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In addition, some members of the PLD superfamily may employ primary alcohols such as ethanol or 1-butanol in the cleavage of the phospholipid, effectively catalyzing the exchange the polar lipid headgroup. Other members of this family are able hydrolyze other phospholipid substrates, such as cardiolipin, or even the phosphodiester bond constituting the backbone of DNA.
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PLFA analysis may be combined with other techniques, such as stable isotope probing to determine which microbes are metabolically active in a sample. PLFA analysis was pioneered by D.C. White at the University of Tennessee, in the early to mid 1980s. Phospholipid bilayer. Each phospholipid consists of a polar hydrophilic head (red) and two hydrophobic fatty acid tails.
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The chemical structure of cholesterol, which differs greatly from a standard phospholipid. The presence of cholesterol exerts a profound but complicated influence on lipid bilayer properties because of its unique physical characteristics. Although it is a lipid, cholesterol bears little resemblance to a phospholipid. The hydrophilic domain of cholesterol is quite small, consisting of a single hydroxyl group.
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One way hemolysin lyses erythrocytes is by forming pores in phospholipid bilayers. Other hemolysins lyse erythrocytes by hydrolyzing the phospholipids in the bilayer.
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D. Papahadjapoulos and N. Miller."Phospholipid Model Membranes I. Structural characteristics of hydrated liquid crystals." Biochimica et Biophysica Acta. 135. (1967) 624-638.
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Phospholipid scramblase 3 is an enzyme that in humans is encoded by the PLSCR3 gene (abbreviated to PLS3 in this section). Like the other phospholipid scramblase family members (PLS1, PLS2, PLS4), PLS3 is a type II plasma membrane protein that is rich in proline and integral in apoptosis, or programmed cell death. The regulation of apoptosis is critical for both cell development and tissue homeostasis Although phospholipid scramblase is thought to exist in all eukaryotic cells, PLS3 is a protein that is novel to the mitochondria. This is very important because mitochondria are central in the apoptotic cell pathway.
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Calcium and phospholipid (a platelet membrane constituent) are required for the tenase and prothrombinase complexes to function. Calcium mediates the binding of the complexes via the terminal gamma-carboxy residues on FXa and FIXa to the phospholipid surfaces expressed by platelets, as well as procoagulant microparticles or microvesicles shed from them. Calcium is also required at other points in the coagulation cascade.
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Chemical structure of MLCL backbone Monolysocardiolipin (MLCL) is a phospholipid with three fatty acid chains located in the inner membrane of mitochondria. MLCL is normally present as part of the metabolic cycle of mitochondrial lipids, such as cardiolipin. It is remodeled by the enzymes monolysocardiolipin acyltransferase, lysocardiolipin acyltransferase, and tafazzin, which transfer a fourth fatty acid chain onto the phospholipid.
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This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain the calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Transcript variants encoding the same isoform have been identified.
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Immunological responses could be the cause in many cases of infertility and miscarriage. Some immunological reasons that contribute to infertility are reproductive autoimmune failure syndrome, the presence of anti-phospholipid antibodies, and antinuclear antibodies. Anti-phospholipid antibodies are targeted toward the phospholipids of the cell membrane. Studies have shown that antibodies against phosphatidylserine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine target the pre-embryo.
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Muller-Roeber B, Pical C. Inositol Phospholipid Metabolism in Arabidopsis. Characterized and Putative Isoforms of Inositol Phospholipid Kinase and Phosphoinositide-Specific Phospholipase C. Plant Physiol 2002 130:22–46 PIPKs are today divided into three groups, type I, II and III that share significant sequence homology but differ in the substrate specificities, subcellular localisations and functions.Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC .
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Antibodies directed against annexin A5 are found in patients with a disease called the antiphospholipid syndrome (APS), a thrombophilic disease associated with autoantibodies against phospholipid compounds. Annexin A5 forms a shield around negatively charged phospholipid molecules. The formation of an annexin A5 shield blocks the entry of phospholipids into coagulation (clotting) reactions. In the antiphospholipid antibody syndrome, the formation of the shield is disrupted by antibodies.
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The foundation of all biomembranes consists of a bilayer structure of phospholipids. The phospholipid molecule is amphipathic; it contains a hydrophilic polar head and a hydrophobic nonpolar tail. The phospholipid heads interact with each other and aqueous media, while the hydrocarbon tails orient themselves in the center, away from water. These latter interactions drive the bilayer structure that acts as a barrier for ions and molecules.
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In enzymology, a phospholipid-hydroperoxide glutathione peroxidase () is an enzyme that catalyzes the chemical reaction :2 glutathione + a lipid hydroperoxide \rightleftharpoons glutathione disulfide + lipid + 2 H2O Thus, the two substrates of this enzyme are glutathione and lipid hydroperoxide, whereas its 3 products are glutathione disulfide, lipid, and H2O. This enzyme belongs to the family of oxidoreductases, to be specific those acting on a peroxide as acceptor (peroxidases). The systematic name of this enzyme class is glutathione:lipid-hydroperoxide oxidoreductase. Other names in common use include peroxidation-inhibiting protein, PHGPX, peroxidation-inhibiting protein: peroxidase, glutathione, (phospholipid hydroperoxide-reducing), phospholipid hydroperoxide glutathione peroxidase, hydroperoxide glutathione peroxidase, or glutathione peroxidase 4 (GPX4).
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Structure of an ether phospholipid. Note ether at first and second positions. Plasmalogen. Note ether at first position, and ester at second position. Platelet-activating factor.
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The C-terminal C2-like PLAT domain binds calcium and allows the toxin to bind to the phospholipid head-groups on the cell surface. The C-terminal domain enters the phospholipid bilayer. The N-terminal domain has phospholipase activity. This property allows hydrolysis of phospholipids such as phosphatidyl choline, mimicking endogenous phospholipase C. The hydrolysis of phosphatidyl choline produces diacylglycerol, which activates a variety of second messenger pathways.
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Under physiological conditions phospholipid molecules in the cell membrane are in the liquid crystalline state. It means the lipid molecules are free to diffuse and exhibit rapid lateral diffusion along the layer in which they are present. However, the exchange of phospholipid molecules between intracellular and extracellular leaflets of the bilayer is a very slow process. Lipid rafts and caveolae are examples of cholesterol-enriched microdomains in the cell membrane.
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The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury.
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The inner mitochondrial membrane contains proteins with three types of functions: # Those that perform the electron transport chain redox reactions # ATP synthase, which generates ATP in the matrix # Specific transport proteins that regulate metabolite passage into and out of the mitochondrial matrix It contains more than 151 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion. Additionally, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in cow hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes.
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The Davson–Danielli model (or paucimolecular model) was a model of the plasma membrane of a cell, proposed in 1935 by Hugh Davson and James Danielli. The model describes a phospholipid bilayer that lies between two layers of globular proteins and It is trilaminar and lipoprotinious. The phospholipid bilayer had already been proposed by Gorter and Grendel in 1925; however, the flanking proteinaceous layers in the Davson–Danielli model were novel and intended to explain Danielli's observations on the surface tension of lipid bilayers (It is now known that the phospholipid head groups are sufficient to explain the measured surface tension). The Davson–Danielli model predominated until Singer and Nicolson advanced the fluid mosaic model in 1972.
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This in vitro diagnostic test is based on the ability of the venom of the Russelli viper to accelerate blood clotting. The venom contains the enzymes RVV-V and RVV-X which activate factor V and factor X, which converts prothrombin into thrombin in the presence of phospholipid and calcium. In the dRVVT assay, low, rate-limiting concentrations of both Russell's viper venom and phospholipid are used to give a standard clotting time of 30 to 40 seconds.(7) This makes the test sensitive to the presence of lupus anticoagulants, because these antibodies interfere with the clot-promoting role of phospholipid in vitro, and their presence results in a prolonged clotting time.
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Occasionally it can also be driven by entropy without energy input, in cases like the formation of the phospholipid bilayer of a cell, where hydrophobic interactions aggregate the molecules.
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Robertson's unit membrane model' was given by J. David Robertson in 1959. This Biomembrane model proposed by Robertson stated that Biomembranes are made up of three layers. Out of these three layers, two are protein layers and one is phospholipid layer. Phospholipid Bilayer is 25-35Å thick and Each of the two Protein layer is 20-25Å thick (Overall 65-85Å) Robertson used electron bombardment on membranes and observed two distinct zones.
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VAV Life Sciences' was rated C2 (2010) & MSME2 (2014) by SMERA, India's first rating agency for SME segment and is a member of International Lecithin & Phospholipid Society, CHEMEXCIL, Federation of Indian Export Organisations, Phospholipid Research Centre and the Indo-German Chamber of Commerce. VAV Life Sciences' employs biotechnologists, chemists, microbiologists, engineers, finance/legal/marketing analysts and general administrators. Around 6% of its employees have PhD degrees and 32% have a master's degree.
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Testicular tissue-derived seipin is essential for male fertility by modulating testicular phospholipid homeostasis. The lack of seipin in germ cells results in complete male infertility and teratozoospermia. Spermatids devoid of seipin in germ cells are morphologically abnormal with large ectopic lipid droplets and aggregate in dysfunctional clusters. Elevated levels of phosphatidic acid accompanied with an altered ratio of polyunsaturated to monounsaturated and saturated fatty acids show impaired phospholipid homeostasis during spermiogenesis .
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The amount of ethanol molecules depend on the concentration of ethanol present in the phospholipid membrane. Force field parameters are measured for the POPC lipids and monovalent ions (Na+, K+, and Cl−), which are very important. A summary of the atomic-scale molecular dynamics simulations is then provided which contains important information as followed: 1) a system number that corresponds to a particular phospholipid simulation 2) the concentration of ethanol mol% used in a particular simulation 3) the concentration of ethanol (v/v%) used for the simulation 3) the ethanol/lipid ratio that is derived from the simulation 4) the area (nm2) of the phospholipid membrane which details the expansion of the membranes as the concentration of ethanol is increased 5) the thickness of the membrane which is based on the distance between the average positions of the phosphorus atoms on opposite sides of the phospholipid membrane and 6) the tilt of the head group of the POPC lipid based on changes in the angle towards the interior region of the phospholipid membrane which was surprisingly not very significant. ;Significance of research: The summary of the POPC simulations described above shows that the POPC system's initial area per lipid value was initially .
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Probable phospholipid-transporting ATPase VA also known as ATPase class V type 10A (ATP10A) or aminophospholipid translocase VA is an enzyme that in humans is encoded by the ATP10A gene.
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Phospholipids are commonly found in the phospholipid bilayer of membranes. They have hydrophilic heads and hydrophopic tails. A protein is another type of macromolecules. Amino acids are the monomers of proteins.
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This 11-mer repeats tract is proposed to anchor the protein to the phospholipid monolayer of lipid droplets for its assembly, though no targeting sequence has yet been found in PLIN4.
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Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.
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There are various types of phospholipids; consequently, their synthesis pathways differ. However, the first step in phospholipid synthesis involves the formation of phosphatidate or diacylglycerol 3-phosphate at the endoplasmic reticulum and outer mitochondrial membrane. The synthesis pathway is found below: Phosphatidic acid synthesis The pathway starts with glycerol 3-phosphate, which gets converted to lysophosphatidate via the addition of a fatty acid chain provided by acyl coenzyme A. Then, lysophosphatidate is converted to phosphatidate via the addition of another fatty acid chain contributed by a second acyl CoA; all of these steps are catalyzed by the glycerol phosphate acyltransferase enzyme. Phospholipid synthesis continues in the endoplasmic reticulum, and the biosynthesis pathway diverges depending on the components of the particular phospholipid.
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After binding to the phospholipid surface, annexin A5 assembles into a trimeric cluster. This trimer consists of three annexin A5 molecules that are bound to each other via non-covalent protein- protein interactions. The formation of annexin A5 trimers results in the formation of a two-dimensional crystal lattice on the phospholipid membrane. This clustering of annexin A5 on the membrane greatly increases the intensity of annexin A5 when labeled with a fluorescent or radioactive probe.
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In the inward facing conformation, the binding site on the A domain is open directly to the surrounding aqueous solutions. This allows hydrophilic molecules to enter the binding site directly from the inner leaflet of the phospholipid bilayer. In addition, a gap in the protein is accessible directly from the hydrophobic core of the inner leaflet of the membrane bilayer. This allows hydrophobic molecules to enter the binding site directly from the inner leaflet of the phospholipid bilayer.
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Possible biomedical-oriented applications of this technique are related to the study of the myelin and myelopathies. Myelin is a highly ordered structure, in which many lipid- enriched, densely compacted phospholipid bilayers are spirally rolled up around the cylindrical axons. The linear acyl chains of the phospholipid molecules present a perpendicular orientation with respect to the myelin surface. Therefore, in a myelinated nerve fiber, a large number of molecular bonds are ordered around a radial axis of symmetry.
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IMPs include transporters, linkers, channels, receptors, enzymes, structural membrane-anchoring domains, proteins involved in accumulation and transduction of energy, and proteins responsible for cell adhesion. Classification of transporters can be found in Transporter Classification Database. As an example of the relationship between the IMP (in this case the bacterial phototrapping pigment, bacteriorhodopsin) and the membrane formed by the phospholipid bilayer is illustrated below. In this case the integral membrane protein spans the phospholipid bilayer seven times.
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Since estrogen is a steroidal hormone, it can pass through the phospholipid membranes of the cell, and receptors therefore do not need to be membrane-bound in order to bind with estrogen.
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A new approach for a blood-brain barrier model based on phospholipid vesicles: Membrane development and siRNA-loaded nanoparticles permability. Journal of Membrane Science. Volume 503. pp. 8–15. Published: March 2016.
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Phosphatidylcholine a major component of egg lecithin, occurs in all cellular organisms, being one of the important components of the phospholipid portion of the cell membrane. Other components include phosphatidylethanolamine and sphingomyelin.
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The generalized reaction for P-type ATPases is: nLigand1 (out) + mLigand2 (in) + ATP → nLigand1 (in) + mLigand2 (out) + ADP + Pi. where the ligand can be either a metal ion or a phospholipid molecule.
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Sec14p exhibits two distinct domains, made up of twelve ⍺-helices, six 𝛽-strands, and eight 310-helices. The phospholipid binding domain of Sec14p consists of a hydrophobic pocket within the carboxy-terminal domain.
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The milk fat globule is surrounded by a phospholipid trilayer containing associated proteins, carbohydrates, and lipids derived primarily from the membrane of the secreting mammary epithelial cell (lactocyte). This trilayer is collectively known as MFGM. While MFGM makes up only an estimated 2% to 6% of the total milk fat globule, it is an especially rich phospholipid source, accounting for the majority of total milk phospholipids. In contrast, the inner core of the milk fat globule is composed predominantly of triacylglycerols.
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PLD-catalyzed hydrolysis has been proposed to occur in two stages via a "ping-pong" mechanism. In this scheme, the histidine residues of each HKD motif successively attack the phospholipid substrate. Functioning as nucleophiles, the constituent imidazole moieties of the histidines form transient covalent bonds with the phospholipid, producing a short-lived intermediate that can be easily hydrolyzed by water in a subsequent step. Substrate presentation; PLD (blue oval) is sequestered into cholesterol- dependent lipid domains (green lipids) by palmitoylation.
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Archaeol is usually found as phospholipid in archaea cells. The synthetic pathway of fully saturated archaeol phospholipid proceeds as follows: the synthesis of isoprenoid side chains by head-to-tail linkage of isoprenes, ether linkage to glycerol-1-phosphate backbone, CDP archaeol formation, polar head group attachment and saturation of double bonds. Following this, tetraether lipids may be synthesized afterwards by dimerization reaction via a head-to-head linkage. Archaea feature different biosynthetic pathways of isoprenoid chains compared to bacteria and eukarya.
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In vitro, Sec14p has been demonstrated to catalyze the transport of phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) between lipid membranes. It has been suggested that the ability to bind PtdIns and PtdCho aids the intracellular transport function and regulation of Sec14p. This property may arise from potential transport of membrane lipids between the endoplasmic reticulum (ER) and the Golgi body by Sec14p to maintain an equilibrium in the membrane lipid concentration. Sec14p is thought to achieve phospholipid transport through phospholipid exchange.
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This irreversibility of the inverted-micelles are supported by mass density profiles which display an overlapping of leaflets from opposite membranes that interact forming a strong interlocking between the acyl chains or hydrophobic region with and without the presence of ethanol. Snapshots of the simulations are produced at 100 ns which compared the phospholipid membrane system in the presence of ethanol and in the absence of ethanol which continues to support ethanol's preference to bind near the hydrophilic region of the phospholipid. The researchers also added monovalent ions as salt ions (NaCl) to the phospholipid membrane system which formed non-lamellar phases (micelles) as well. This phenomenon is important because they predict that in the presence of ethanol the micelles can serve as transporters for hydrophilic structures across the membrane.
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C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The biological function of this gene has not yet been determined.
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Ebselen is a potent scavenger of hydrogen peroxide as well as hydroperoxides including membrane bound phospholipid and cholesterylester hydroperoxides. Several ebselen analogs have been shown to scavenge hydrogen peroxide in the presence of thiols.
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To make carbon nanotubes soluble in water, phospholipids such as lysoglycerophospholipids have been used. The single phospholipid tail wraps around the carbon nanotube, but the double tailed phospholipids did not have the same ability.
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Neomycin binds to the 30S subunit of the ribosome and inhibits translation of proteins from mRNA. Neomycin exhibits a high binding affinity for phosphatidylinositol 4,5-bisphosphate (PIP2), which is a phospholipid component of cell membranes.
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The C5bC6 complex is bound by C7. This junction alters the configuration of the protein molecules exposing a hydrophobic site on C7 that allows the C7 to insert into the phospholipid bilayer of the pathogen.
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Probable phospholipid-transporting ATPase IC is an enzyme that in humans is encoded by the ATP8B1 gene. This protein is associated with progressive familial intrahepatic cholestasis type 1 as well as benign recurrent intrahepatic cholestasis.
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Choline kinase catalyzes the formation of phoshocholine, the committed step in phosphatidylcholine biosynthesis. Phosphatidylcholine is the major phospholipid in eukaryotic membranes. Phosphatidylcholine is important for a variety of function in eukaryotes such as facilitating the transport of cholesterol through the organism, acting as a substrate for the production of second messengers and as a cofactor for the activity of several membrane- related enzymes. CK also plays a vital role in the production of sphingomyelin, another important membrane phospholipid and in the regulation of cell growth.
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NISCH has been shown to interact with IRS4, Integrin alpha 5, and small GTPases Rac1, Rab4a, Rab9a, Rab14 and Rab38 in GTP-bound form. NISCH also interacts with phospholipid PI(3)P via its PX domain.
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Molecular Cell Biology. 5th ed. W.H. Freeman and Company New York, 2004. 535–539. The phospholipid bilayer is a two-layer structure mainly composed of phospholipids, which are amphiphilic molecules that have hydrophilic and hydrophobic regions.
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Biochim Biophys Acta. 1334, 1-4. GPI anchors consist of a phosphoethanolamine linker that binds to the C-terminus of target proteins. Glycan's core structure has a phospholipid tail that anchors the structure to the membrane.
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Interfacial Water Facilitates Energy Transfer by Inducing Extended Vibrations in Membrane Lipids, J. Phys. Chem. B, 2012, 116 (22), pp 6455–6460 Mashaghi A et al. Enhanced Autoionization of Water at Phospholipid Interfaces. J. Phys. Chem.
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The phospholipid bilayer is most permeable to small, uncharged solutes. Protein channels float through the phospholipids, and, collectively, this model is known as the fluid mosaic model. Aquaporins are protein channel pores permeable to H2O water.
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Alkylphosphocholines are phospholipid-like molecules that have been synthesised, which have remarkable biological and therapeutic activities. They are phosphocholine esters of aliphatic long chain alcohols differing in chain length, unsaturation and position of the cis-double bond.
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Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.
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Without the shield, there is an increased quantity of phospholipid molecules on cell membranes, speeding up coagulation reactions and causing the blood-clotting characteristic of the antiphospholipid antibody syndrome. Annexin A5 showed upregulation in papillary thyroid carcinoma.
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The Biology of the Mycobacteria. London: Academic, 1982. Print. After oleic acid is esterified to a phospholipid, S-adenosyl-methionine donates a methyl group to the double bond of oleic acid.Kubica, George P., and Lawrence G. Wayne.
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The research also suggests that ethanol enhances the association between cholesterol-phospholipids within the liquid-ordered bilayers. The mechanism on how ethanol induces the liquid- disorder phase as well as enhances the cholesterol-phospholipid association is still not understood. The researchers have mentioned that part of the liquid- disorder formation occurs possibly be interrupting the hydrophobic region of the phospholipids, by binding closely towards the hydrophilic region of the phospholipid, and acting as "filler" since ethanol cannot closely align with the neighboring phospholipids. All of these possible mechanisms can be contributed to ethanol's amphiphilic nature.
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The presence of enzymes involved in phospholipid biosynthesis in MAM fraction is known since the 1970s, and the synthesis of some phospholipid is completed in both organelles. For instance, the biosynthetic pathway of phosphatidylcholine involves different steps some on the ER and some on the inner mitochondrial membrane. Connerth et al. identified Ups1 as a yeast LTP that can shuttle phosphatidic acid (PA) between mitochondrial membranes: they showed that effective lipid transfer required the interaction of Ups1 with Mdm35 to convert phosphatidic acid into cardiolipin in the inner membrane.
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The inositol-sensitive upstream activation sequence (UAS) has a consensus sequence 5'-CATGTGAAAT-3' and is present in the promoter regions of genes that encode enzymes of phospholipid biosynthesis. These enzymes are regulated by inositol and choline, both of which are phospholipid precursors. Within this consensus sequence, the first six bases are homologous with canonical binding motif for proteins within the bHLH or the basic helix-loop-helix family. Studies have shown that Ino2p and Ino4p, two bHLH regulatory proteins from Saccharomyces cerevisiae, bind to promoter fragments containing this element of the consensus sequence.
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The phospholipids are amphiphilic. The hydrophilic end usually contains a negatively charged phosphate group, and the hydrophobic end usually consists of two "tails" that are long fatty acid residues. In aqueous solutions, phospholipids are driven by hydrophobic interactions that result in the fatty acid tails aggregating to minimize interactions with water molecules. The result is often a phospholipid bilayer: a membrane that consists of two layers of oppositely oriented phospholipid molecules, with their heads exposed to the liquid on both sides, and with the tails directed into the membrane.
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All species of Thermomonosporaceae share the same cell wall type (type III; meso- diaminopimelic acid), a similar menaquinone profile in which MK-9(H6)is predominant, and fatty acid profile type 3a. The presence of the diagnostic sugar madurose is variable, but can be found in most species of this family. The polar lipid profiles are characterized as phospholipid type PI for most species of Thermomonospora, Actinomadura and Spirillospora. The members of Actinocorallia are characterized by phospholipid type PII. The G+C content of the DNA lies within the range 66±72 mol%.
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Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid.
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Hardeman, H. van den Bosch, Topography of ether phospholipid biosynthesis, Biochim. Biophys. Acta 1006 (1989) 1–8. The first step of the biosynthesis is catalyzed by GNPAT. This enzyme acylates dihydroxyacetone phosphate (DHAP) at the sn-1 position.
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He became interested in blood clotting after his son required heart surgery. He also collaborated with Whitman chemistry professor David Frasco, using phospholipid bilayers as a model to study the surface of living cells and their absorption processes.
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These subunits are displayed in the attached image. SdhA is green, SdhB is teal, SdhC is fuchsia, and SdhD is yellow. Around SdhC and SdhD is a phospholipid membrane with the intermembrane space at the top of the image.
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The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles, whose NMR structure was recently published; the complexes are capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-binding cassette transporter A1 (ABCA1). A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually causing the newly synthesized HDL to assume a spherical shape. HDL particles increase in size as they circulate through the bloodstream and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, for example by the interaction with the ABCG1 transporter and the phospholipid transport protein (PLTP). HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals, ovary, and testes by both direct and indirect pathways.
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Rosing J, Bevers EM, Comfurius P, Hemker HC, von Dieijen G, Weiss HJ, et al. Impaired factor X and prothrombin activation associated with decreased phospholipid exposure in platelets from a patient with a bleeding disorder. Blood 1985; 65:1557-1561.
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Biological molecules are amphiphilic or amphipathic, i.e. are simultaneously hydrophobic and hydrophilic. The phospholipid bilayer contains charged hydrophilic headgroups, which interact with polar water. The layers also contain hydrophobic tails, which meet with the hydrophobic tails of the complementary layer.
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15-lipoxygenase acts by binding to phospholipids and yields hydroperoxy and epoxy metabolites. One such metabolite, 15-hydroxyeicosatetranoic acid (15-HETE), is released intracellularly, where it conjugates to phosphatidylethanolamine, a phospholipid component. 15-HETE-PE induces expression of the mucin MUC5AC.
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This residue is found in VDAC1 and VDAC2 but not VDAC3. The side chain of this charged residue points into the phospholipid bilayer which would normally cause repulsive forces to occur. E73 however, has been implicated in VDAC1 function and interaction.
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Some Gram-positive bacteria also encode a soluble diacylglycerol kinase capable of reintroducing DAG into the phospholipid biosynthesis pathway. DAG accumulates in Gram- positive bacteria as a result of the transfer of glycerol-1-phosphate moieties from phosphatidylglycerol to lipotechoic acid.
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The capability to bind to the SecB chaperone during post- translational translocation, the ribosome (during both post-translational translocation and co-translational translocation ) and the phospholipid bilayer is important for SecA functioning and is achieved by the C-terminal linker domain.
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The biosynthesis of sterculic acid begins with the cyclopropanation of the alkene of phospholipid-bound oleic acid, an 18-carbon cis-monounsaturated fatty acid. This transformation involves two mechanistic steps: electrophilic methylation with S-adenosyl methionine to give a carbocationic reactive intermediate, followed by cyclization via loss of H+ mediated by a cyclopropane-fatty-acyl-phospholipid synthase enzyme. The product, dihydrosterculic acid, is converted to sterculic acid by dehydrogenation of the cis-disubstituted cyclopropane to cyclopropene. An additional step of α oxidation removes one carbon from the carboxy chain to form the 17-carbon-chain structure of malvalic acid.
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This leads to the surrounding of the droplet in a phospholipid monolayer that allows it to disperse within the aqueous cytoplasm. In the next stage, lipid droplets then migrate to the apical surface of the cell, where plasma membrane subsequently envelops the droplet and extrudes together with it. It fully encases the fat droplet in an additional bilayer of phospholipids. The milk fat globule thus released into the glandular lumen, measuring 3-6 μm in average diameter, is surrounded by a phospholipid trilayer containing associated proteins, carbohydrates, and lipids derived primarily from the membrane of the secreting lactocyte.
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Figure (1) The Arachidonic acid cascade, showing biosynthesis of AA's eicosanoid products. EPA and DGLA compete for the same pathways, moderating the actions of AA and its products. In the arachidonic acid cascade, dietary linoleic acid (18:2 ω-6) is desaturated and elongated to form arachidonic acid (and also other omega 6), esterified into a phospholipid in the cell membrane. Next, in response to many inflammatory stimuli, such as air pollution, smoking, second- hand smoke, hydrogenated vegetable oils and other exogenous toxins; phospholipase is generated and cleaves this phospholipid, releasing AA as a free fatty acid.
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Fig. 1 Components of a Virosome A virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid membrane (either a mono- or bi-layer) vesicle incorporating virus derived proteins to allow the virosomes to fuse with target cells. Viruses are infectious agents that can replicate in their host organism, however virosomes do not replicate. The properties that virosomes share with viruses are based on their structure; virosomes are essentially safely modified viral envelopes that contain the phospholipid membrane and surface glycoproteins. As a drug or vaccine delivery mechanism they are biologically compatible with many host organisms and are also biodegradable.
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It is an artificial chemical compound, commonly used as a food additive, for instance as a solvent in flavourings, and for its humectant function, with E number E1518 and Australian approval code A1518. It is used as an excipient in pharmaceutical products, where it is used as a humectant, a plasticizer, and as a solvent. The plasticizing capabilities of triacetin have been utilized in the synthesis of a biodegradable phospholipid gel system for the dissemination of the cancer drug paclitaxel (PTX). In the study, triacetin was combined with PTX, ethanol, a phospholipid and a medium chain triglyceride to form a gel-drug complex.
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The NEDD4 protein has a modular structure that is shared among the NEDD4 family, consisting of an amino-terminal C2 calcium-dependent phospholipid binding domain, 3-4 WW protein-protein interaction domains, and a carboxyl-terminal catalytic HECT ubiquitin ligase domain. The C2 domain targets proteins to the phospholipid membrane, and can also be involved in targeting substrates. The WW domains interact with proline rich PPxY motifs in target proteins to mediate interactions with substrates and adaptors. The catalytic HECT domain forms a thioester bond with activated ubiquitin transferred from an E2 ubiquitin conjugating enzyme, before transferring ubiquitin directly to a specific substrate.
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Almaida-Pagan and coworkers found that mitochondrial membrane lipid composition changes with age, when studying Turquoise killifish. The proportion of monosaturated fatty acids decreased with age, and the proportion of polysaturated fatty acids increased. The overall phospholipid content also decreased with age.
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This region is usually very thermodynamically stable and occurs only in the phospholipid membrane between cells. The intracellular domain is the serine/threonine kinase domain. In this domain, phosphorylation catalyzes a protein kinase cascade leading to a response.Shiu, S.H., and Bleecker, A.B. (2001).
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This newly found member of the scramblase family is "responsible for phospholipid translocation between two lipid compartments," the inner mitochondrial membrane and the outer membrane. Further experimental evidence suggests that the mechanism and effectors of PLS3's enzymatic activity are rather nuanced.
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Significant activity can be detected in the faeces. The substrates of ENPP family vary greatly. Some have activity against nucleotides, some have activity against phospholipid and lysophospholipids. ENPP7 is the only enzyme that has a type of phospholipase C activity against sphingomyelin.
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Phosphatidylcholine transfer protein (PCTP) also known as StAR-related lipid transfer domain protein 2 (STARD2) is a specific intracellular phospholipid binding protein that can transfer phosphatidylcholine between different membranes in the cytosol. In humans, phosphatidylcholine transfer protein is encoded by the PCTP gene.
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The lipids were fractionated on a solid-phase extraction column and the neutral lipids, free fatty acids and other materials discarded and the phospholipid phase then dried, prior esterification to form the fatty acid methyl esters (FAMEs) to make them suitable for analysis.
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Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via apoptotic mimicry.
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The phospholipid bilayer structure (fluid mosaic model) with specific membrane proteins accounts for the selective permeability of the membrane and passive and active transport mechanisms. In addition, membranes in prokaryotes and in the mitochondria and chloroplasts of eukaryotes facilitate the synthesis of ATP through chemiosmosis.
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Common sources of industrially produced phospholipids are soya, rapeseed, sunflower, chicken eggs, bovine milk, fish eggs etc. Each source has a unique profile of individual phospholipid species as well as fatty acids and consequently differing applications in food, nutrition, pharmaceuticals, cosmetics and drug delivery.
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Phosphatidylinositol transfer protein alpha isoform is a protein that in humans is encoded by the PITPNA gene. Phosphatidylinositol transfer proteins are a diverse set of cytosolic phospholipid transfer proteins that are distinguished by their ability to transfer phospholipids between membranes in vitro (Wirtz, 1991).
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"A sensitive test demonstrating lupus anticoagulant and its behavioural patterns". British Journal of Haematology. 40 (1): 143-51. Kaolin is the surface activator, and the test also requires small amounts of cell fragments and plasma lipids to provide the phospholipid surface required for coagulation.
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A proteomics approach using two-dimensional chromatography-mass spectrometry found major phospholipids were archaeol phosphatidylglycerol, archaeol phosphatidylinositol, hydroxyarchaeol phosphatidylglycerol, and hydroxyarchaeol phosphatidylinositol. All phospholipid classes contained a series of unsaturated analogues, with the degree of unsaturation dependent on phospholipid class. The proportion of unsaturated lipids from cells grown at 4 °C was significantly higher than for cells grown at 23 °C. 3-Hydroxy-3-methylglutaryl coenzyme A synthase, farnesyl diphosphate synthase, and geranylgeranyl diphosphate synthase were identified in the expressed proteome, and most genes involved in the mevalonate pathway and processes leading to the formation of phosphatidylinositol and phosphatidylglycerol were identified in the genome sequence.
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The mechanism(s) by which microorganisms are killed and/or inactivated by defensins is not understood completely. However, it is generally believed that killing is a consequence of disruption of the microbial membrane. The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them to insert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged (mostly cationic) regions interact with anionic phospholipid head groups and water. Subsequently, some defensins can aggregate to form 'channel-like' pores; others might bind to and cover the microbial membrane in a 'carpet-like' manner.
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Further, both the tubules and the helices were made rigid by creating them from phospholipid like monomers, such that the overall polymer could be manipulated by a magnetic field. In her doctoral thesis, Schürle used her previous findings and experience in CNT characterization, magnetic field-based servoing system, and maneuverable nanostructures to create NanoMag, a magnetic control system enabling the manipulation of microstructures that meets the needs of biological application. NanoMag was designed to allow magnetic control of spheres, cylinders, and helices, all potential drug-carrier structures. To complement this technology, Schürle also designed a method to create helical microswimmers based on a self-assembly mechanism similar to the phospholipid bilayer.
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Phosphomonoesters (or phosphoric esters) are chemical compounds containing one ester bond and a phosphate group. In biology, phosphomonesters are needed as the building blocks for the synthesis of Phospholipid cellular membranes, especially those found on neurons. Enzymes which cleave these bonds are known as phosphomonoesterases, or phosphatases.
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"The Bacillus subtilis desaturase: a model to understand phospholipid modification and temperature sensing." Archives of Microbiology 183.4 (2005):229-35. All desaturases require oxygen and ultimately consume NADH even though desaturation is an oxidative process. Desaturases are specific for the double bond they induce in the substrate.
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ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub- family ABCA), also known as the cholesterol efflux regulatory protein (CERP) is a protein which in humans is encoded by the ABCA1 gene. This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis.
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An example of a phosphatidylcholine, a type of phospholipid in egg lecithin. Red - choline and phosphate group; Black - glycerol; Green - unsaturated fatty acid; Blue - saturated fatty acid Egg lecithin is a type of lecithin, a group of compounds primarily containing phospholipids, that is derived from eggs.
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Ribosomes are sometimes referred to as organelles, but the use of the term organelle is often restricted to describing sub-cellular components that include a phospholipid membrane, which ribosomes, being entirely particulate, do not. For this reason, ribosomes may sometimes be described as "non-membranous organelles".
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The basic concept is that the phospholipid content represents living organisms as these compounds are rapidly decomposed in aerobic mixed communities and that some of the neutral lipid components such as the lipopolysaccharides of Gram-negative bacteria do not reflect organisms alive at the time of sampling.
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This is opposed to the intrinsic (amplification) pathway, which involves both activated factor IX and factor VIII. Both pathways lead to the activation of factor X (the common pathway), which combines with activated factor V in the presence of calcium and phospholipid to produce thrombin (thromboplastin activity).
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Spectroscopic investigations on the binding site of bovine hepatic fatty-acid binding protein: evidence for the existence of a single binding site for two fatty-acid molecules. Chemistry and Physics of Lipids 38(1-2): 159-174. lipid transport processes including structural characterization of lipoproteins, and phospholipid-transfer proteins.
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Vitamin K deficiency from other causes (e.g., in malabsorption) or impaired vitamin K metabolism in disease (e.g., in liver failure) lead to the formation of PIVKAs (proteins formed in vitamin K absence), which are partially or totally non-gamma carboxylated, affecting the coagulation factors' ability to bind to phospholipid.
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The atomic-scale molecular dynamics simulations are used to monitor the changes in the phospholipid membrane. All the simulations are carried out using GROMACS simulation suite software along with other methods that are essential to perform the simulations. The temperature and pressure are controlled at 310K and 1bar.
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Phosphatidylcholine, a type of phospholipid in lecithin. The lecithin–sphingomyelin ratio (a.k.a. L-S or L/S ratio) is a test of fetal amniotic fluid to assess for fetal lung immaturity. Lungs require surfactant, a soap-like substance, to lower the surface pressure of the alveoli in the lungs.
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After cell stimulation, including apoptosis, a subsequent cytosolic Ca2+ increase promotes the loss of phospholipid asymmetry of the plasma membrane, subsequent phosphatidylserine exposure, and a transient phospholipidic imbalance between the external leaflet at the expense of the inner leaflet, leading to budding of the plasma membrane and microvesicle release.
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Vaccari I, Dina G, Tronchère H, Kaufman E, Chicanne G, Cerri F, Wrabetz L, Payrastre B, Quattrini A, Weisman LS, Meisler MH, Bolino A. Genetic interaction between MTMR2 and FIG4 phospholipid phosphatases involved in Charcot-Marie-Tooth neuropathies. PLoS Genet. 2011 Oct;7(10):e1002319. Epub 2011 Oct 20.
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Nonionic surfactants are able to bind to both proteins and phospholipid membrane, leading to leakage of low molecular mass compounds by increasing the permeability of membranes and vesicles. This may result in serious damage in cells or even cell death.Ivanković, T., & Hrenović, J. (2010). Surfactants in the environment.
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The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
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In plants, phosphorus (P) is considered second to nitrogen as the most essential nutrient to ensure health and function. Phosphorus is used by plants in numerous processes such as photophosphorylation, genetic transfer, the transportation of nutrients, and phospholipid cell membranes.International Plant Nutrition Institute. (1999). Functions of phosphorus in plants.
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The liquid ordered phase is a liquid crystalline phase of a lipid bilayer, and is of significant biological importance. It occurs in many lipid mixtures combining cholesterol with a phospholipid and/or sphingolipids e.g. sphingomyelin. This phase has been related to lipid rafts that may exist in plasma membranes.
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Breton A (1893) État mental dans la chorée. Thèse, Paris, no. 124., possibly the result of the extreme sleep disorder. This form of chorea was caused by streptococcal infections, which at present respond to antibiotics; it still occurs as a result of systemic lupus or anti-phospholipid syndromes.
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Differential scanning calorimetry results have shown that MP196 prefers incorporation into bacterial cell membranes over erythrocyte membranes, as this cationic peptide prefers incorporating into membranes which have a higher negatively charged phospholipid ratio. Erythrocytes are made up of neutral phospholipid, thus explaining why MP196 does not get incorporated into its membrane, because MP196 prefers negatively charged cytoplasmic membranes, it has a low hemolytic activity, and thus has low toxicity against humans. Incorporation of MP196 into the cell membrane causes detachment of cytochrome C and MurG proteins from the membrane. Cytochrome C is a protein involved in the bacterial respiratory chain and MurG is an enzyme involved in the bacterial cell wall biosynthesis pathway.
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"The structure and stability of phospholipid bilayers by atomic force microscopy." Biophysical Journal. 68. (1995) 171-8.) must be used to avoid damage. This consideration is particularly important when studying metastable systems such as vesicles adsorbed on a substrate, since the AFM tip can induce rupture and other structural changes.
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1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon is an enzyme that in humans is encoded by the AGPAT5 gene. This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis.
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This suggests a carpet mechanism for cell lysis. The carpet mechanism is when a high density of peptides accumulates on the target membrane surface. The phospholipid displacement changes in fluidity, and the cellular contents leak out. The presence of anionic lipids or cholesterol was found to reduce the peptide's ability to disrupt bilayers.
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Myelin is a phospholipid membrane that wraps around axons to provide them with insulation. It is produced by Schwann cells in the PNS, and by oligodendrocytes in the CNS. Myelin clearance is the next step in Wallerian degeneration following axonal degeneration. The cleaning up of myelin debris is different for PNS and CNS.
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Annexin A1 belongs to the annexin family of Ca2+-dependent phospholipid-binding proteins that have a molecular weight of approximately 35,000 to 40,000 Dalton and are preferentially located on the cytosolic face of the plasma membrane. Annexin A1 protein has an apparent relative molecular mass of 40 kDa with phospholipase A2 inhibitory activity.
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The loss of asymmetry, in particular the appearance of the anionic phospholipid phosphatidylserine on the exoplasmic face, can serve as an early indicator of apoptosis. This effect has been observed in neurons as a response to amyloid beta peptides, thought to be a primary cause of the neurodegenerative effects of Alzheimer's disease.
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Thermodesulfobacterium hveragerdense has a phospholipid bilayer membrane. The lipids of the membrane are mainly dietherglycerophospholipids(DEG-P), but there are also many diacylglycerophospholipids(DAG-P) and acyl/etherglycerophospholipids(AEG-P) in the lipid bilayer as well. The bilayer also contains minute amounts of diphosphatidylglycerol (DPG) compounds in it, mainly phosphatidylethanolamine, phosphatidylinositol, and aminopentanetetral.
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Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group. It is the main constituent of pulmonary surfactants, which reduces the work of breathing and prevents alveolar collapse during breathing. It also plays an important role in the study of liposomes and human bilayers.
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Type II phosphatidate phosphatases are transmembrane enzymes found mainly in the plasma membrane. They can dephosphorylate other substrates besides phosphatidate, and therefore are also known as lipid phosphate phosphatases. Their main role is in lipid signaling and in phospholipid head-group remodeling. One example of a type II phosphatidate phosphatase is PgpB (PDBe: 5jwy).
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Phosphatidylserine is a phospholipid—more specifically a glycerophospholipid—which consists of two fatty acids attached in ester linkage to the first and second carbon of glycerol and serine attached through a phosphodiester linkage to the third carbon of the glycerol. Phosphatidylserine sourced from plants differs in fatty acid composition from that sourced from animals.
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Channels can also respond to membrane thickness. An amphipathic helix that runs along the inner membrane of TREK-1 channels is thought to sense changes in membrane thickness and gate the channel. PEth is a phospholipid metabolite of ethanol that builds up in the membrane of nerves and competitively inhibits PIP2 activation of K+ channels.
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A fluid membrane model of the phospholipid bilayer. The lipid bilayer consists of two layers- an outer leaflet and an inner leaflet. The components of bilayers are distributed unequally between the two surfaces to create asymmetry between the outer and inner surfaces. This asymmetric organization is important for cell functions such as cell signaling.
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Cabezon feed on crustaceans, mollusks, fish and fish eggs. Cabezon are taken as a game fish, however their roe is toxic to humans, because of the occurrence of a toxic phospholipid (Dinogunellin). Cabezon inhabit the tops of rocky ledges as opposed to rockfish and lingcod, which usually inhabit the sheer faces of these features.
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Mutations in misfire and Fer-1, ferlins in flies and C. elegance, cause male sterility because of defects in fertilization. Function of ferlin proteins involves employing multiple domains. C2A domains are specialized in lipid binding. The phospholipid interaction is often calcium dependent as C2 domains have evolved to respond to increase in calcium concentration.
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At the bottom is the common phospholipid, phosphatidylcholine.Voet (2005), Ch. 12 Lipids and Membranes. Lipids comprise a diverse range of molecules and to some extent is a catchall for relatively water-insoluble or nonpolar compounds of biological origin, including waxes, fatty acids, fatty-acid derived phospholipids, sphingolipids, glycolipids, and terpenoids (e.g., retinoids and steroids).
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Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain (a phospholipid-binding motif) or through protein–protein interactions with membrane-associated protein complexes Some members of this family have been shown to facilitate protein sorting.
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Supplementation with citicoline can increase the amount of choline available for acetylcholine synthesis and aid in rebuilding membrane phospholipid stores after depletion. Citicoline decreases phospholipase stimulation. This can lower levels of hydroxyl radicals produced after an ischemia and prevent cardiolipin from being catabolized by phospholipase A2. It can also work to restore cardiolipin levels in the inner mitochondrial membrane.
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The outer mitochondrial membrane, which encloses the entire organelle, is 60 to 75 angstroms (Å) thick. It has a protein-to-phospholipid ratio similar to that of the cell membrane (about 1:1 by weight). It contains large numbers of integral membrane proteins called porins. A major trafficking protein is the pore-forming voltage-dependent anion channel (VDAC).
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Even though bacteria are prokaryotic cells just like Archaea, their membranes are made of phospholipid bilayers. Cyanobacteria and mycoplasmas are two examples of bacteria. They characteristically do not have ether linkages like Archaea, and they are grouped into a different category—and hence a different domain. There is a great deal of diversity in this domain.
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NPP catalyses the nucleophilic substitution of one ester bond on a phosphodiester substrate. It has a nucleoside binding pocket that excludes phospholipid substrates from the active site. A threonine nucleophile has been identified through site-directed mutagenesis, and the reaction inverts the stereochemistry of the phosphorus center. The sequence of bond breakage and formation has yet to be resolved.
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Laurdan is an organic compound which is used as a fluorescent dye when applied to fluorescence microscopy. It is used to investigate membrane qualities of the phospholipid bilayers of cell membranes. One of its most important characteristics is its sensitivity to membrane phase transitions as well as other alterations to membrane fluidity such as the penetration of water.
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Specialized transmembrane proteins recognize the substance and allow it to move across the membrane when it otherwise would not, either because the phospholipid bilayer of the membrane is impermeable to the substance moved or because the substance is moved against the direction of its concentration gradient.Active Transport Process . Buzzle.com (2010-05-14). Retrieved on 2011-12-05.
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The SERAC1 gene encodes for a protein necessary for phosphatidylglycerol remodeling. phosphatidylglycerol remodeling is a process of altering or remodeling a particular phospholipid called phosphatidylglycerol. Phosphatidylglycerol helps make cardiolipin, an important ingredient that surrounds the Inner mitochondrial membrane. Cardiolipin is responsible for converting energy acquired from food to a cell- usable form and required for proper mitochondrial function.
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Motivation for (+)-totarol functioning via disruption of membrane structure is due to its high phospholipid/water partition coefficient. However, (+)-totarol's partitioning capability was only observed at concentrations 10 to 100 fold higher than required for antibacterial activity. Thus it is unlikely that (+)-totarol is an uncoupler of bacterial respiration at the low levels observed in antimicrobial studies.
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Diagram displays a solid lipid nanoparticle (SLN). There is only one phospholipid layer because the interior of the particle is solid. Molecules such as antibodies, targeting peptides, and drug molecules can be bound to the surface of the SLN. Also, solid lipid nanoparticles (SLNs) are lipid nanoparticles with a solid interior as shown in the diagram on the right.
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Microvesicle membranes consist mainly of membrane lipids and membrane proteins. Regardless of their cell type of origin, nearly all microvesicles contain proteins involved in membrane transport and fusion. They are surrounded by a phospholipid bilayer composed of several different lipid molecules. The protein content of each microvesicle reflects the origin of the cell from which it was released.
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Tyrocidine has a unique mode of action in which it disrupts the cell membrane function, making it a favorable target for engineering derivatives. Tyrocidine appears to perturb the lipid bilayer of a microbe's inner membrane by permeating the lipid phase of the membrane. The exact affinity and location of tyrocidine within the phospholipid bilayer is not yet known.
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This gene encodes a member of the membrane- bound O-acyltransferases family of integral membrane proteins that have acyltransferase activity. The encoded protein is a lysophosphatidylinositol acyltransferase that has specificity for arachidonoyl-CoA as an acyl donor. This protein is involved in the re-acylation of phospholipids as part of the phospholipid remodeling pathway known as the Land cycle.
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In high temperatures, cholesterol inhibits the movement of phospholipid fatty acid chains, causing a reduced permeability to small molecules and reduced membrane fluidity. The opposite is true for the role of cholesterol in cooler temperatures. Cholesterol production, and thus concentration, is up-regulated (increased) in response to cold temperature. At cold temperatures, cholesterol interferes with fatty acid chain interactions.
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Phospholipid arrangement in cell membranes. Phosphatidylcholine is the major component of lecithin. It is also a source for choline in the synthesis of acetylcholine in cholinergic neurons. Phospholipids (PL) are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group, and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue.
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That is the dominant structural motif of the membranes of all cells and of some other biological structures, such as vescicles or virus coatings. Phospholipid bilayers are the main structural component of cell membranes. In biological membranes, the phospholipids often occur with other molecules (e.g., proteins, glycolipids, sterols) in a bilayer such as a cell membrane.
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The combination provides fluidity in two dimensions combined with mechanical strength against rupture. Purified phospholipids are produced commercially and have found applications in nanotechnology and materials science. The first phospholipid identified in 1847 as such in biological tissues was lecithin, or phosphatidylcholine, in the egg yolk of chickens by the French chemist and pharmacist Theodore Nicolas Gobley.
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The extracellular forms of phospholipases A2 have been isolated from different venoms (snake, bee, and wasp), from virtually every studied mammalian tissue (including pancreas and kidney) as well as from bacteria. They require Ca2+ for activity. Pancreatic sPLA2 serve for the initial digestion of phospholipid compounds in dietary fat. Venom phospholipases help to immobilize prey by promoting cell lysis.
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Common fatty acids include lauric acid, stearic acid, and oleic acid. The study and engineering of lipids typically focuses on the manipulation of lipid membranes and encapsulation. Cellular membranes and other biological membranes typically consist of a phospholipid bilayer membrane, or a derivative thereof. Along with the study of cellular membranes, lipids are also important molecules for energy storage.
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Methylcobalamin and 5-methyltetrahydrofolate are needed by methionine synthase in the methionine cycle to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine, thereby generating tetrahydrofolate (THF) and methionine, which is used to make SAMe. SAMe is the universal methyl donor and is used for DNA methylation and to make phospholipid membranes, choline, sphingomyelin, acetylcholine, and other neurotransmitters.
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The NEDD4-2 protein consists of an amino-terminal Ca2+-phospholipid binding domain (C2), 4 WW domains (protein-protein interaction domains) and the carboxyl-terminal HECT domain (ubiquitin ligase domain). The WW domains in the protein are responsible for binding the substrates, regulatory proteins and adaptors. These domains generally recognize PPxY (or similar) motifs in the target proteins.
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This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol.
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The large changes in the Ca2+-concentrations interfere with many processes, including vesicle fusion and the mitochondrial membrane potential. Both these processes are important for acetylcholine homeostasis.Rigoni, Michela, et al (2007). "Calcium Influx and Mitochondrial Alterations at Synapses Exposed to Snake Neurotoxins or Their Phospholipid Hydrolysis Products", Journal of Biological Chemistry, 282(15), 11238–11245. doi:10.1074/jbc.m610176200.
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Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity.
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PAF is a potent activator of platelet aggregation, inflammation, and anaphylaxis. It is similar to the ubiquitous membrane phospholipid phosphatidylcholine except that it contains an acetyl-group in the SN-2 position and the SN-1 position contains an ether- linkage. PAF signals through a dedicated G-protein coupled receptor, PAFR and is inactivated by PAF acetylhydrolase.
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Decapacitation factor (DF) is composed of factors in seminal plasma which modulates the fertilizing ability of spermatozoa. The activity is achieved by interaction between cholesterol, phospholipids and fibronectin-like substances and delivered via small vesicles in seminal plasma. DF prevents onset of capacitation. Physiologically it is achieved through spermatozoal membrane stabilization by maintaining physiological cholesterol/phospholipid ratio.
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Neurotransmitters are synthesized in the axon terminal where they are stored in vesicles. These neurotransmitter-filled vesicles are the quanta that will be released into the synapse. Quantal vesicles release their contents into the synapse by binding to the presynaptic membrane and combining their phospholipid bilayers. Individual quanta may randomly diffuse into the synapse and cause a subsequent MEPP.
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Phospholipid is available as an independent reagent or in combination with tissue factor as thromboplastin. Complete thromboplastin consists of tissue factor, phospholipids (since platelets were removed from blood sample being tested), and CaCl2 to reintroduce calcium ions which were chelated by sodium citrate originally used to prevent coagulation of the sample blood during transportation and/or storage.
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Myristoylation is thus a form of "molecular switch." Both hydrophobic myristoyl groups and "basic patches" (highly positive regions on the protein) characterize myristoyl-electrostatic switches. The basic patch allows for favorable electrostatic interactions to occur between the negatively charged phospholipid heads of the membrane and the positive surface of the associating protein. This allows tighter association and directed localization of proteins.
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Xkr8 was activated directly by caspases and required a caspase-3 cleavage site for its function. CED-8, the only Caenorhabditis elegans Xk-family homolog, also promoted apoptotic PtdSer exposure and cell-corpse engulfment. Thus, Xk-family proteins have evolutionarily conserved roles in promoting the phagocytosis of dying cells by altering the phospholipid distribution in the plasma membrane. Chen et al.
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The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors.
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In collaboration with Steven Karlish at the Weizmann Institute, Stein investigated the kinetic mechanism of active Na and K ion transport, confirming the basic alternating access model of active Na and K transport. Karlish SJ, Stein WD. Effects of ATP or phosphate on passive rubidium fluxes mediated by Na-K-ATPase reconstituted into phospholipid vesicles. J Physiol. 1982; 328: 317–31.
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Academic Press, 1993. 1–7 They surround cells and organelles with a semi-permeable barrier that prevents free flow of substances. The membrane consists of a phospholipid bilayer structure and often embedded or otherwise associated proteins, along with cholesterol and glycolipids.Lodish, Harvey; Berk, Arnold; Matsudaira, Paul; Berk, Arnold; Matsudaira, Paul; Kaiser, Chris A.; Krieger, Monty; Scott, Matthew P.; Zipursky, S. Lawrence; Darnell, James.
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Tafazzin is a protein that in humans is encoded by the TAZ gene. Tafazzin is highly expressed in cardiac and skeletal muscle, and functions as a phospholipid-lysophospholipid transacylase (it belongs to phospholipid:diacylglycerol acyltransferases). It catalyzes remodeling of immature cardiolipin to its mature composition containing a predominance of tetralinoleoyl moieties. Several different isoforms of the tafazzin protein are produced from the TAZ gene.
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Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases (PLSCRs) constitute a family of five homologous proteins that are named as hPLSCR1–hPLSCR5. Scramblases are not members of the general family of transmembrane lipid transporters known as flippases. Scramblases are distinct from flippases and floppases.
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C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmannin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling.
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This fluid lipid bilayer cross section is made up entirely of phosphatidylcholine. The three main structures phospholipids form in solution; the liposome (a closed bilayer), the micelle and the bilayer. The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells.
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The remodeling pathway is activated by inflammatory agents and it is thought to be the primary source of PAF under pathological conditions. The de novo pathway is used to maintain PAF levels during normal cellular function. The most common pathway taken to produce PAF is remodeling. The precursor to the remodeling pathway is a phospholipid, which is typically phosphatidylcholine (PC).
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Annexin A8-like protein 2 is a protein that in humans is encoded by the ANXA8L2 gene. This gene encodes a member of the annexin family of evolutionarily conserved Ca2+ and phospholipid binding proteins. The encoded protein may function as an anticoagulant that indirectly inhibits the thromboplastin-specific complex. Overexpression of this gene has been associated with acute myelocytic leukemia.
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Antimicrobial peptide resistance and lipid A acylation protein PagP is a family of several bacterial antimicrobial peptide resistance and lipid A acylation (PagP) proteins. The bacterial outer membrane enzyme PagP transfers a palmitate chain from a phospholipid to lipid A. In a number of pathogenic Gram-negative bacteria, PagP confers resistance to certain cationic antimicrobial peptides produced during the host innate immune response.
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In addition, strong hydrophobic phospholipid-peptide interactions have been discovered in both models. In the two peptide models, the folded parts of the carrier molecule correlate to the hydrophobic domain, although the rest of the molecule remains unstructured. 400px Cell-penetrating peptide facilitated translocation is a topic of great debate. Evidence has been presented that translocation could use several different pathways for uptake.
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Zygote formation is a crucial step in sexual reproduction, and it is reliant on the fusion of sperm and egg cells. Consequently, these cells must be primed to gain fusion-competence. Phosphatidylserine is a phospholipid that usually resides on the inner layer of the cell membrane. After sperm cells are primed, phosphatidylserine can be found on the outer leaflet of the membrane.
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This increased connectivity also caused an abnormality in Ca+2 signaling between neurons. Also with regard to the role in MAMs in phospholipid metabolism, patients diagnosed with AD have been reported to show alterations in levels of Phosphatedylserine and phostphatedylethanolamine in the ER and mitochondria respectively, this leads to the intracellular tangles containing hyperphosphorylated forms of the microtubule‐associated protein tau within tissues.
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The inner membrane of mitochondria is similar in lipid composition to the membrane of bacteria. This phenomenon can be explained by the endosymbiont hypothesis of the origin of mitochondria as prokaryotes internalized by a eukaryotic host cell. In pig heart mitochondria, phosphatidylethanolamine makes up the majority of the inner mitochondrial membrane at 37.0% of the phospholipid composition. Phosphatidylcholine makes up about 26.5%, cardiolipin 25.4%, and phosphatidylinositol 4.5%.
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The inner membrane is a phospholipid bilayer that contains the complexes of oxidative phosphorylation. which contains the electron transport chain that is found on the cristae of the inner membrane and consists of four protein complexes and ATP synthase. These complexes are complex I (NADH:coenzyme Q oxidoreductase), complex II (succinate:coenzyme Q oxidoreductase), complex III (coenzyme Q: cytochrome c oxidoreductase), and complex IV (cytochrome c oxidase).
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The different types of beta-ketoacyl-ACP synthases in type II FAS are called FabB, FabF, and FabH synthases. FabH catalyzes the quintessential ketoacyl synthase reaction with malonyl ACP and acetyl CoA. FabB and FabF catalyze other related reactions. Given that their function is necessary for proper biological function surrounding lipoprotein, phospholipid, and lipopolysaccharide synthesis, they have become a target in antibacterial drug development.
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It has been found LACTB could cause obesity through gene co- expression analysis based on data integrated from multiple sources. This has been validated in vivo through LACTB overexpression in transgenic mice, which resulted in an obese phenotype. LACTB has also been identified to be a tumor suppressor through its effect on mitochondrial phospholipid metabolism and modulation of cell differentiation state.Keckesova et al. 2017.
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Cavin-2 or Serum deprivation-response protein (SDPR) is a protein that in humans is encoded by the SDPR gene. Cavin-2 is highly expressed in a variety of human endothelial cells. This gene encodes a calcium-independent phospholipid-binding protein whose expression increases in serum-starved cells. This protein has also been shown to be a substrate for protein kinase C (PKC) phosphorylation.
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In molecular biology, proteins in the antifungal protein family consist of five antiparallel beta strands which are highly twisted creating a beta barrel stabilised by four internal disulphide bridges. A cationic site adjacent to a hydrophobic stretch on the protein surface may constitute a phospholipid binding site. Human Epithelium produce antifungal proteins. The proteins kill fungi by inducing apoptosis and/or forming pores on the cell membrane.
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The hydrophobic core of the phospholipid bilayer is constantly in motion because of rotations around the bonds of lipid tails. Hydrophobic tails of a bilayer bend and lock together. However, because of hydrogen bonding with water, the hydrophilic head groups exhibit less movement as their rotation and mobility are constrained. This results in increasing viscosity of the lipid bilayer closer to the hydrophilic heads.
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Choline kinase beta (CK), also known as Ethanolamine kinase (EK), Choline kinase-like protein , choline/ethanolamine kinase beta (CKEKB), or Choline/ethanolamine kinase is a protein encoded by the CHKB gene. This gene is found on chromosome 22 in humans. The encoded protein plays a key role in phospholipid biosynthesis. Choline kinase (CK) and ethanolamine kinase (EK) catalyzes the first step in phosphatidylethanolamine biosynthesis.
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The human gene ATP8B3 encodes the protein ATPase, aminophospholipid transporter, class I, type 8B, member 3. The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. This gene encodes the member 3 of the phospholipid- transporting ATPase 8B.
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Scheme of a liposome formed by phospholipids in an aqueous solution Mifamurtide is muramyl tripeptide phosphatidylethanolamine (MTP-PE), a synthetic analogue of muramyl dipeptide. The side chains of the molecule give it a longer elimination half-life than the natural substance. The substance is applied encapsulated into liposomes (L-MTP-PE). Being a phospholipid, it accumulates in the lipid bilayer of the liposomes in the infusion.
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ZP3 is a glycoprotein present in zona pelucida and it interacts with receptors in spermatozoon. So, ZP3 can activate G protein coupled receptors and tyrosine kinase receptors, that leads to production of PLC. PLC cleaves the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate. IP3 is released as a soluble structure into the cytosol and DAG remains bound to the membrane.
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Alpha-synuclein forms an extended helical structure on small unilamellar vesicles. A preferential binding to small vesicles has been found. The binding of alpha-synuclein to lipid membranes has complex effects on the latter, altering the bilayer structure and leading to the formation of small vesicles. Alpha-synuclein has been shown to bend membranes of negatively charged phospholipid vesicles and form tubules from large lipid vesicles.
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Cellulose is synthesized by cellulose synthase or Rosette terminal complexes which reside on a cells membrane. As cellulose fibrils are synthesized and grow extracellularly they push up against neighboring cells. Since the neighboring cell can not move easily the Rosette complex is instead pushed around the cell through the fluid phospholipid membrane. Eventually this results in the cell becoming wrapped in a microfibril layer.
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Milk lipids are secreted in a unique manner by lactocytes, which are specialized epithelial cells within the alveoli of the lactating mammary gland. The process takes place in multiple stages. First, fat synthesized within the endoplasmic reticulum accumulates in droplets between the inner and outer phospholipid monolayers of the endoplasmic reticulum membrane. As these droplets increase in size, the two monolayers separate further and eventually pinch off.
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" The egg yolk contributes proteins, fats, and emulsifiers to the dough. Emulsifying agents are essential to doughnut formation because they prevent the fat molecules from separating from the water molecules in the dough. The main emulsifier in egg yolk is called lecithin, which is a phospholipid. "The fatty acids are attracted to fats and oils (lipids) in food, while the phosphate group is attracted to water.
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This protein is a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. This protein functions as an autocrine factor which heightens osteoclast formation and bone resorption. Epigenetic regulation of Annexin A2 has been identified as a key determinant of mesenchymal transformation in brain tumors.
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Many of phospholipase D’s cellular functions are mediated by its principal product, phosphatidic acid (PA). PA is a negatively charged phospholipid, whose small head group promotes membrane curvature. It is thus thought to facilitate membrane-vesicle fusion and fission in a manner analogous to clathrin-mediated endocytosis. PA may also recruit proteins that contain its corresponding binding domain, a region characterized by basic amino acid-rich regions.
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For example, enzyme action can be explained in terms of the shape of a pocket in the protein molecule that matches the shape of the substrate molecule or its modification due to binding of a metal ion. Similarly the structure and function of the biomembranes may be understood through the study of model supramolecular structures as liposomes or phospholipid vesicles of different compositions and sizes.
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Phospholipid synthesis occurs in the cytosolic side of ER membrane that is studded with proteins that act in synthesis (GPAT and LPAAT acyl transferases, phosphatase and choline phosphotransferase) and allocation (flippase and floppase). Eventually a vesicle will bud off from the ER containing phospholipids destined for the cytoplasmic cellular membrane on its exterior leaflet and phospholipids destined for the exoplasmic cellular membrane on its inner leaflet.
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Studies have shown that an increase in the supply of Dissolved Oxygen results in an increased production of DHA. In addition to oxygen concentration, C. cohnii is known to react to a change in salinity by changing their growth rate. C. cohnii's growth is highly dependent on their microbiome or environment. Most of the DHA in the Microalgae is found in the phospholipid, phosphatidylcholine.
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Virosomes are vehicles that have a spherical shape with a phospholipid mono/bilayer membrane. Inside of the virosome, there is a central cavity that holds the therapeutic molecules such as nucleic acids, proteins, and drugs. On the surface of the virosome, there can be different types of glycoproteins. Glycoproteins are a type of protein that have an oligosaccharide chain bonded to amino acid chains.
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Sphaerosomes(=spherosomes) or Oleosomes are small cell organelles bounded by single membrane which take part in storage and synthesis of lipid. They were discovered by Perner. They are only found in plant cells. They arise from endoplasmic reticulum and are surrounded by a single but half unit membrane with phospholipid monolayer having polar heads towards the cytosol and hydrophobic tails towards the inner side.
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The influx of Ca2+ inside the cell triggers negative feedback mechanisms to suppress TRPV6 activity and prevent Ca2+ overload. TRPV6 channel activity is regulated by the intracellular level of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) and interactions with Ca2+-Calmodulin (CaM) complex. The depletion of PIP2 or CaM-binding inactivates TRPV6. The influx of Ca2+ in TRPV6 expressing cells activates phospholipase C (PLC) which in turn hydrolyzes PIP2.
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Phospholipid liposomes are used as targeted drug delivery systems. Hydrophilic drugs can be carried as solution inside the SUVs or MLVs and hydrophobic drugs can be incorporated into lipid bilayer of these liposomes. If injected into circulation of human/animal body, MLVs are preferentially taken up phagocytic cells, and thus drugs can be targeted to these cells. For general or overall delivery, SUVs may be used.
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Chaikoff did research on the physiological biochemistry of blood transport involved in lipid and carbohydrate metabolism and metabolic disturbances associated with diabetes and vascular disease (such as arteriosclerosis). He used radioactive phosphorus (phosphorus-32) to investigate phospholipid metabolism. He used radioactive carbon (carbon-14) to investigate lipogenesis and the biosynthesis and utilization of fatty acids, sterol-containing metabolites, glucose, glycogen, adrenal steroids, and thyroid hormones.
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This gene encodes a multi-pass transmembrane protein that belongs to the anoctamin family. This protein is an essential component for the calcium-dependent exposure of phosphatidylserine on the cell surface. The scrambling of phospholipid occurs in various biological systems, such as when blood platelets are activated, they expose phosphatidylserine to trigger the clotting system. Mutations in this gene are associated with Scott syndrome.
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The sPLA2 domain has the ability to bind a phospholipid, but does not have enzymatic capability. Presumably the domain also binds calcium Ca2+ ions and carbonate CO32+. Otoconin-90 would position the ions to fit into a calcite lattice. The calcium is hypothesized to be secreted from the sensory epithelium into the gelatinous substance on the top of which it meets otoconin and forms otoconia.
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Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid with two 16-carbon saturated chains and a phosphate group with quaternary amine group attached. The DPPC is the strongest surfactant molecule in the pulmonary surfactant mixture. It also has higher compaction capacity than the other phospholipids, because the apolar tail is less bent. Nevertheless, without the other substances of the pulmonary surfactant mixture, the DPPC's adsorption kinetics is very slow.
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Interactions between hydrophobic amino-acid residues and the adjacent membranes cause destabilization of the membranes. This allows the phospholipids in the outer layer of each membrane to interact with each other. The outer leaflets of the two membranes form a hemifusion stalk to minimize energetically unfavorable interactions between hydrophobic phospholipid tails and the environment. This stalk expands, allowing the inner leaflets of each membrane to interact.
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The phospholipid bilayer that forms the cell surface membrane consists of a hydrophobic inner core region sandwiched between two regions of hydrophilicity, one at the inner surface and one at the outer surface of the cell membrane (see lipid bilayer article for a more detailed structural description of the cell membrane). The inner and outer surfaces, or interfacial regions, of model phospholipid bilayers have been shown to have a thickness of around 8 to 10 Å, although this may be wider in biological membranes that include large amounts of gangliosides or lipopolysaccharides. The hydrophobic inner core region of typical biological membranes may have a thickness of around 27 to 32 Å, as estimated by Small angle X-ray scattering (SAXS). The boundary region between the hydrophobic inner core and the hydrophilic interfacial regions is very narrow, at around 3Å, (see lipid bilayer article for a description of its component chemical groups).
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The clotting times of both the initial dRVVT assay and confirmatory test are normalized and then used to determine a ratio of time without phospholipid excess to time with phospholipid excess. In general, a ratio of greater than 1.3 is considered a positive result and implies that the patient may have antiphospholipid antibodies. The dRVVT test has a higher specificity than the aPTT test for the detection of lupus anticoagulant, because it is not influenced by deficiencies or inhibitors of clotting factors VIII, IX or XI as the venom mainly activates only factors V and X. However dRVVT tests are strongly affected by the new direct oral anticoagulants (DOACs) and false positive LA results are obtained particularly with rivaroxaban. It is now possible to specifically remove DOACs from test plasmas with activated carbon and enable the correct diagnosis of LA with the dRVVT system despite their initial presence.
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Cholesterol is an important lipid involved in metabolism, cell function, and structure. It is a structural component of the cell membrane, such that it provides structure and regulates the fluidity of the phospholipid bilayer. Furthermore, cholesterol is a constituent in lipid rafts. These are congregations of proteins and lipids (including sphingolipids and cholesterol) that float within the cell membrane, and play a role in the regulation of membrane function.
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Previous studies showed that LPE, a natural phospholipid, can accelerate ripening and prolong shelf life of tomato fruit,Farag KM, Palta JP, Physiol Plant. 87(1993) 515-521 and retard senescence in attached and detached leaves and fruit of tomato.Farag KM, Palta JP, Hort Technol, 3(1993) 62-65 In other studies, LPE inhibited the activity of phospholipase D (PLD), a membrane degrading enzyme, of which active is increased during senescence.
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The synthesis of the phospholipids contained in pulmonary surfactant takes place in the endoplasmic reticulum of type II pneumocytes. Pulmonary surfactant has both protein and lipid components. More specifically, it has been found that phosphatidylcholine (PC) is the most abundant phospholipid (70%–85%), and that PC is primarily present as dipalmitoylphosphatidylcholine (DPPC). De novo synthesis of phosphatidylcholine in the lung arises primarily from cytidine diphosphate-choline (CDP-choline).
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This phospholipid is found in a solid/gel phase at 37 °C (at the effective temperature of the human body). Its melting point is around 41.3 °C. Therefore, when the temperature is above 41 °C, DPPC is no longer found in a gel phase but in a liquid one. When in contact with silica surfaces, it has been demonstrated that DPPC bilayers have different properties depending on the temperature.
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1-acyl-sn-glycerol-3-phosphate acyltransferase gamma is an enzyme that in humans is encoded by the AGPAT3 gene. The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene.
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TIM14 is required for the ATP-dependent import of mitochondrial pre-proteins into the mitochondrial matrix. The J-domain of TIM14 stimulates mtHsp70 ATPase activity to power this transport. Additionally, TIM14 helps regulate mitochondrial morphology by complexing with prohibitins to perform disphosphoglycerolipid cardiolipin (CL) remodeling. CL is a key phospholipid in mitochondrial membranes that modulates the fusion and fission of mitochondrial membranes, as well as mitophagy and apoptosis.
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SEC23-interacting protein is a protein that in humans is encoded by the SEC23IP gene. COPII-coated vesicles are involved in protein transport from the Endoplasmic Reticulum to the Golgi Apparatus. The protein encoded by this gene was identified by its interaction with a mouse protein similar to yeast Sec23p, an essential component of the COPII. This protein shares significant similarity with phospholipid-modifying proteins, especially phosphatidic acid preferring-phospholipase A1.
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Glycerol-3-phosphate acyltransferase 1, mitochondrial is an enzyme that in humans is encoded by the GPAM gene. Glycerol-3-phosphate acyltransferase (GPAT; EC 2.3.1.15), which catalyzes the initial and committing step in glycerolipid biosynthesis, is predicted to play a pivotal role in the regulation of cellular triacylglycerol and phospholipid levels. Two mammalian forms of GPAT have been identified on the basis of localization to either the endoplasmic reticulum or mitochondria.
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Phosphatidylserine is the most abundant anionic phospholipid in the cell's plasma membrane, and is usually positioned internally. However, during apoptosis and several pathological conditions including tumorigenesis or infection by some types of viruses, phosphatidylserine is flipped from an internal to an external position. When external, it can potentially be recognized by antibodies. As such, targeting external phosphatidylserine may be a strategy for novel broad-spectrum anti- viral therapies.
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Mutations in CHKB have been found to result in mitochondrial deficiencies and associated disorders. Knockdown of the gene has been known to result in decreased choline kinase and phosphatidylcholine activity. This impairment in activity may lead to a modified composition of the phospholipid composition in the mitochondrial membrane resulting in major disorders in the function and structure of the mitochondria. Major disorders include as Megaconial Congenital Muscular Dystrophy (MDCMC), and Narcolepsy.
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The cooperative unit size is the number of adjacent bases that tend to unwind as a single unit due to the effects of positive cooperativity. This phenomenon applies to other types of chain molecules as well, such as the folding and unfolding of proteins and in the "melting" of phospholipid chains that make up the membranes of cells. Subunit cooperativity is measured on the relative scale known as Hill's Constant.
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This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. The specific function of this gene has not yet been determined; however, it is associated with the plasma membranes of undifferentiated, proliferating endothelial cells and differentiated villus enterocytes. Alternatively spliced transcript variants encoding different isoforms have been identified.
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The different yolk's proteins have distinct roles. Phosvitins are important in sequestering calcium, iron, and other cations for the developing embryo. Phosvitins are one of the most phosphorylated (10%) proteins in nature; the high concentration of phosphate groups provides efficient metal-binding sites in clusters. Lipovitellins are involved in lipid and metal storage, and contain a heterogeneous mixture of about 16% (w/w) noncovalently bound lipid, most being phospholipid.
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They are a subclass of eicosanoids and form the prostanoid class of fatty acid derivatives. The prostaglandins are synthesized in the cell membrane by the cleavage of arachidonate from the phospholipids that make up the membrane. This is catalyzed either by phospholipase A2 acting directly on a membrane phospholipid, or by a lipase acting on DAG (diacyl-glycerol). The arachidonate is then acted upon by the cyclooxygenase component of prostaglandin synthase.
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Since the human body contains mostly water, the ability to deliver hydrophobic drugs effectively in humans is a major therapeutic benefit of nanocarriers. Micelles are able to contain either hydrophilic or hydrophobic drugs depending on the orientation of the phospholipid molecules. Some nanocarriers contain nanotube arrays allowing them to contain both hydrophobic and hydrophilic drugs. One potential problem with nanocarriers is unwanted toxicity from the type of nanomaterial being used.
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For example, the carboxylation of glutamate allows for better binding of calcium cations, and collagen contains hydroxyproline, generated by hydroxylation of proline. Another example is the formation of hypusine in the translation initiation factor EIF5A, through modification of a lysine residue. Such modifications can also determine the localization of the protein, e.g., the addition of long hydrophobic groups can cause a protein to bind to a phospholipid membrane.
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PLA2 enzymes are commonly found in mammalian tissues as well as arachnid, insect, and snake venom. Venom from both snakes and insects is largely composed of melittin, which is a stimulant of PLA2. Due to the increased presence and activity of PLA2 resulting from a snake or insect bite, arachidonic acid is released from the phospholipid membrane disproportionately. As a result, inflammation and pain occur at the site.
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The same fold is shared by Bacterial Permeability Inducing proteins (examples: BPIFP1 BPIFP2 BPIFA3 and BPIFB4), phospholipid transfer protein (PLTP), and long-Palate Lung, and Nasal Epithelium protein (L-PLUNC). The fold is similar to intracellular SMP domains, and originated in bacteria. The crystal structure of CETP has been obtained with bound CETP inhibitors. However, this has not resolved the doubt over whether CETP function as a lipid tube or shuttle.
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The mechanism seems to vary with different organisms and is not well understood. However, pentamidine is suspected to work through various methods of interference of critical functions in DNA, RNA, phospholipid and protein synthesis. Pentamidine binds to adenine-thymine- rich regions of the Trypanosoma parasite DNA, forming a cross-link between two adenines four to five base pairs apart. The drug also inhibits topoisomerase enzymes in the mitochondria of Pneumocystis jirovecii.
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Symptoms can include various movement disorders, neuropsychiatric issues, seizures, visual disturbances, and cognitive decline, usually in different combinations. The cause of NBIA disorders are a multitude of possible mutations in genes directly involved in iron metabolism, and/or impaired phospholipid, and/or ceramide metabolism, and/or lysosomal disorders, as well as mutations in genes with unknown functions. Onset can occur at different ages, from early childhood to late adulthood.
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In this way, β-adrenoceptor molecule is likely a glycoprotein that has N-linked carbohydrate chains. The binding characteristics of 3H-dihydroalprenolol also allowed researchers to understand the importance of anionic and cationic charges of glycocalyx, phospholipid or protein in rat brains. This was discovered by analyzing the relationship between polymeric effectors, DNA, heparin, polymyxin B, histone, gelatin, colominic acid and bovine serum albumin (BSA) and the affinity of β-adrenoceptor.
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Scramblases, flippases, and floppases are three different types of enzymatic groups of phospholipid transportation enzymes. The inner-leaflet, facing the inside of the cell, contains negatively charged amino-phospholipids and phosphatidylethanolamine. The outer-leaflet, facing the outside environment, contains phosphatidylcholine and sphingomyelin. Scramblase is an enzyme, present in the cell membrane, that can transport (scramble) the negatively charged phospholipids from the inner-leaflet to the outer-leaflet, and vice versa.
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Annexin A3 is a protein that in humans is encoded by the ANXA3 gene. It is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increase risk of birth defects in these ART. This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways.
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Other common protein domains function as Serine O-acetyltransferase, Cyclopropane-fatty-acyl-phospholipid synthase, S-adenosylmethionine-dependent methyltransferase or glycosyltransferase. It was observed that many of these genes are related to sulfur metabolism or to methionine metabolism, and therefore sul1 RNAs' function might relate to these pathways. If sul1 RNAs function by sensing ions such as sulfate or metabolites involved in these pathways, they would qualify as riboswitches.
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2-Arachidonoylglycerol is synthesized from arachidonic acid- containing diacylglycerol (DAG), which is derived from the increase of inositol phospholipid metabolism by the action of diacylglycerol lipase. The molecule can also be formed from pathways like the hydrolysis derived (by diglyceride) from both phosphatidylcholine (PC) and phosphatidic acid (PAs) by the action of DAG lipase and the hydrolysis of arachidonic acid-containing lysophosphatidic acid by the action of a phosphatase.
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Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles. The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature is deleterious to the cell and would eventually lead to cell death.
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Franz undertook research in many areas during his time at Monsanto. Some of his other chemistry research includes antiauxin chemistry (isothiazoles, isoxazoles, pyrazoles), plant chemistry, cell membrane chemistry (glyceride and phospholipid syntheses, liposomes), plant hormone chemistry (abscissic acid analogs, ethylene generators), and nitride sulfide chemistry. He also performed research pertaining to reaction mechanisms, coenzyme A antimetabolites, biorational design of herbicides, and periselective addition reactions of one- and threedipoles, as well as fundamental organic research.
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A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins. The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion. They are: # the outer mitochondrial membrane, # the intermembrane space (the space between the outer and inner membranes), # the inner mitochondrial membrane, # the cristae space (formed by infoldings of the inner membrane), and # the matrix (space within the inner membrane).
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The basis for the defect in PS translocation is, at present, unknown. A candidate protein, scramblase,Sims PJ, Wiedmer T. Unraveling the mysteries of phospholipid scrambling. Thromb Haemost 2001; 86:266-275 that may be involved in this process appears to be normal in Scott syndrome platelets.Zhou Q, Sims PJ, Wiedmer T. Expression of proteins controlling transbilayer movement of plasma membrane phospholipids in the B lymphocytes from a patient with Scott syndrome.
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Monolayers have a multitude of applications both at the air-water and at air-solid interphases. Nanoparticle monolayers can be used to create functional surfaces that have for instance anti-reflective or superhydrophobic properties.. Monolayers are frequently encountered in biology. A micelle is a monolayer, and the phospholipid lipid bilayer structure of biological membranes is technically two monolayers. Langmuir monolayers are commonly used to mimic cell membrane to study the effects of pharmaceuticals or toxins.
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While initially studied as a cancer medication, due to side effects it was never used for this purpose. Phospholipid group alkylphosphocholine were known since the early 1980s, particularly in terms of their binding affinity with cobra venom. In 1987 the phospholipids were found to be potent toxins on leukemic cell culture. Initial in vivo investigation on the antineoplastic activity showed positive result, but then only at high dosage and at high toxicity.
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Factor V protein consists of six domains: A1-A2-B-A3-C1-C2. The A domains are homologous to the A domains of the copper- binding protein ceruloplasmin, and form a triangular as in that protein. A copper ion is bound in the A1-A3 interface, and A3 interacts with the plasma. The C domains belong to the phospholipid-binding discoidin domain family (unrelated to C2 domain), and the C2 domain mediates membrane binding.
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When rhodopsin (Rh) absorbs a photon of light its chromophore, 11-cis-3-hydroxyretinal, is isomerized to all-trans-3-hydroxyretinal. Rh undergoes a conformational change into its active form, metarhodopsin. Metarhodopsin activates Gq, which in turn activates a phospholipase Cβ (PLCβ) known as NorpA. PLCβ hydrolyzes phosphatidylinositol (4,5)-bisphosphate (PIP2), a phospholipid found in the cell membrane, into soluble inositol triphosphate (IP3) and diacylglycerol (DAG), which stays in the cell membrane.
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The domain is extracellular, meaning it is on the outside of the cell and it contains two conserved cysteines that form a disulphide bridge. This domain is Wnt binding in WIF, and it has been suggested that RYK may also bind to Wnt. More specifically, crystal structure of WIF-1(WD) show a binding site for phospholipid; two acyl chains extending deep into the domain, and a head group is exposed to the surface.
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The phospholipid bilayer is formed due to the aggregation of membrane lipids in aqueous solutions. Aggregation is caused by the hydrophobic effect, where hydrophobic ends come into contact with each other and are sequestered away from water. This arrangement maximises hydrogen bonding between hydrophilic heads and water while minimising unfavorable contact between hydrophobic tails and water. The increase in available hydrogen bonding increases the entropy of the system, creating a spontaneous process.
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In effect, the GTP turnover of G proteins is greatly increased by mastoparan. These properties of the toxin follow from the fact that it structurally resembles activated G protein receptors when placed in a phospholipid environment. The resultant G protein-mediated signaling cascade leads to intracellular IP3 release and the resultant influx of Ca2+. Research has shown that Mastoparan inhibits all developmental forms of Trypanosoma cruzi, the parasite that is responsible for Chagas disease.
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In addition to genetic changes to bile salt transport molecules, high levels of estrogen glucuronides have been shown to inhibit the bile salt export pump (BSEP) ABCB11, and high levels of progesterone to inhibit the ABCB4 (MDR3) phospholipid transporter. Consequently, both genetic mutations in hepatocyte proteins involved in bile secretion together with inhibition of those proteins by high levels of hormone metabolites in pregnancy may have roles in the pathogenesis of ICP.
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His laboratory at the University of Chicago mostly uses theoretical techniques, such as classical molecular dynamics, to understand the functioning of biological systems at the molecular level. His research has investigated structure, dynamics, and the function of biological macromolecular systems such as ion channels, receptors, and protein kinases. He is a pioneer in the study of membrane proteins using molecular dynamics with explicit phospholipid molecules and solvent.Ion transport in a model gramicidin channel.
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The chemical structure of the outer membrane lipopolysaccharides is often unique to specific bacterial strains (i.e. sub- species) and is responsible for many of the antigenic properties of these strains. As a phospholipid bilayer, the lipid portion of the outer membrane is largely impermeable to all charged molecules. However, channels called porins are present in the outer membrane that allow for passive transport of many ions, sugars and amino acids across the outer membrane.
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The phospholipid bilayer of the cell membrane is, in itself, highly impermeable to ions. The complete structure of the cell membrane includes many proteins that are embedded in or completely cross the lipid bilayer. Some of those proteins allow for the highly specific passage of ions, ion channels. Leak potassium channels allow potassium to flow through the membrane in response to the disparity in concentrations of potassium inside (high concentration) and outside the cell (low).
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Amphipathic Lipid Packing Sensor (ALPS) motifs were first identified in 2005 in ARFGAP1 and have been reviewed. adsorb to) curved lipid bilayers. The curving of a phospholipid bilayer, for example into a liposome, causes disturbances to the packing of the lipids on the side of the bilayer that has the larger surface area (the outside of a liposome for example). The less "ordered" or "looser" packing of the lipids is recognized by ALPS motifs.
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When the extracellular environment is more acidic than the neutral pH within the cell, certain acids will exist in their neutral form and will be membrane soluble, allowing them to cross the phospholipid bilayer. Acids that lose a proton at the intracellular pH will exist in their soluble, charged form and are thus able to diffuse through the cytosol to their target. Ibuprofen, aspirin and penicillin are examples of drugs that are weak acids.
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Members of the genus are not characterized chemotaxonomically by type III/B cell walls (meso-diaminopimelic acid and madurose are present) with peptidoglycan structures of the acetyl type. The predominant menaquinone types are MK-9(H4), MK-9(H6) and MK-9(H8). The phospholipid pattern is PI (diphosphatidylglycerol and phosphatidylinositol are present as major phospholipids) and the fatty acid pattern is type 3a (branched saturated and unsaturated fatty acids plus tuberculostearic acid).
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Glycolipid Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connections that allow cells to connect to one another to form tissues. Glycolipids are found on the surface of all eukaryotic cell membranes, where they extend from the phospholipid bilayer into the extracellular environment.
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There are no simple methods available for analysis of phospholipids since the close range of polarity between different phospholipid species makes detection difficult. Oil chemists often use spectroscopy to determine total Phosphorus abundance and then calculate approximate mass of phospholipids based on molecular weight of expected fatty acid species. Modern lipid profiling employs more absolute methods of analysis, with nuclear magnetic resonance spectroscopy (NMR spectroscopy), particularly 31P-NMR, while HPLC-ELSD provides relative values.
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The PEMT enzyme converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) via three sequential methylations by S-adenosyl methionine (SAM). The enzyme is found in endoplasmic reticulum and mitochondria-associated membranes. It accounts for ~30% of PC biosynthesis, with the CDP-choline, or Kennedy, pathway making ~70%. PC, typically the most abundant phospholipid in animals and plants, accounts for more than half of cell membrane phospholipids and approximately 30% of all cellular lipid content.
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The diversity of sequences and structures flanking the calcium-coordinating amino acid residues renders the eight synaptotagmins bind to calcium at various affinities, covering the full range of calcium requirements for regulated exocytosis. The C2A domain regulates the fusion step of synaptic vesicle exocytosis. Consistent with this, the kinetics of Ca2+-dependent phospholipid binding activity of the C2A domain in vitro are compatible with the very fast nature of neurotransmitter release (within 200 μs).
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In cancer cells, the ratio between dimeric and tetrameric forms of PKM2 determines what happens to glucose carbons. If PKM2 is in the dimeric form, glucose is channeled into synthetic processes such as nucleic acid, amino acid, or phospholipid synthesis. If A-Raf is present, PKM2 is more likely to be in the tetrameric form. This causes more glucose carbons to be converted to pyruvate and lactate, producing energy for the cell.
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Omega−3 fatty acids occur naturally in two forms, triglycerides and phospholipids. In the triglycerides, they, together with other fatty acids, are bonded to glycerol; three fatty acids are attached to glycerol. Phospholipid omega−3 is composed of two fatty acids attached to a phosphate group via glycerol. The triglycerides can be converted to the free fatty acid or to methyl or ethyl esters, and the individual esters of omega−3 fatty acids are available.
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PLC-β then cleaves a specific plasma membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG remains bound to the membrane, and IP3 is released as a soluble molecule into the cytoplasm. IP3 diffuses to bind to IP3 receptors, a specialized calcium channel in the endoplasmic reticulum (ER). These channels are specific to calcium and only allow the passage of calcium from the ER into the cytoplasm.
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Annexin A7 is a protein that in humans is encoded by the ANXA7 gene. Annexin VII is a member of the annexin family of calcium-dependent phospholipid binding proteins. The Annexin VII gene contains 14 exons and spans approximately 34 kb of DNA. An alternatively spliced cassette exon results in two mRNA transcripts of 2.0 and 2.4 kb which are predicted to generate two protein isoforms differing in their N-terminal domain.
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31P-NMR(nuclear magnetic resonance) spectroscopy is widely used for studies of phospholipid bilayers and biological membranes in native conditions. The analysis of 31P-NMR spectra of lipids could provide a wide range of information about lipid bilayer packing, phase transitions (gel phase, physiological liquid crystal phase, ripple phases, non bilayer phases), lipid head group orientation/dynamics, and elastic properties of pure lipid bilayer and as a result of binding of proteins and other biomolecules.
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If there is only one phospholipid bilayer, they are called unilamellar liposome vesicles; otherwise they are called multilamellar. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.
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Water molecules travel through the plasma membrane, tonoplast membrane (vacuole) or protoplast by diffusing across the phospholipid bilayer via aquaporins (small transmembrane proteins similar to those responsible for facilitated diffusion and ion channels). Osmosis provides the primary means by which water is transported into and out of cells. The turgor pressure of a cell is largely maintained by osmosis across the cell membrane between the cell interior and its relatively hypotonic environment.
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Prior to entry, a virus must attach to a host cell. Attachment is achieved when specific proteins on the viral capsid or viral envelope bind to specific proteins called receptor proteins on the cell membrane of the target cell. A virus must now enter the cell, which is covered by a phospholipid bilayer, a cell's natural barrier to the outside world. The process by which this barrier is breached depends upon the virus.
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This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within the endoplasmic reticulum membrane and converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. Mutations in this gene have been associated with congenital generalized lipodystrophy, a disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
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Cell membranes require high levels of cholesterol – typically an average of 20% cholesterol in the whole membrane, increasing locally in raft areas up to 50% cholesterol (- % is molecular ratio).de Meyer F, Smit B. Effect of cholesterol on the structure of a phospholipid bilayer. Proc Natl Acad Sci U S A 2009; 106: 3654-8. It associates preferentially with sphingolipids (see diagram) in cholesterol-rich lipid rafts areas of the membranes in eukaryotic cells.
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Phospholipid-derived fatty acids (PLFAs) are widely used in microbial ecology as chemotaxonomic markers of bacteria and other organisms. Phospholipids are the primary lipids composing cellular membranes. Phospholipids can be saponified, which releases the fatty acids contained in their diglyceride tail. Once the phospholipids of an unknown sample are saponified, the composition of the resulting PLFA can be compared to the PLFA of known organisms to determine the identity of the sample organism.
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GJA1 is a 43.0 kDa protein composed of 382 amino acids. GJA1 contains a long C-terminal tail, an N-terminal domain, and multiple transmembrane domains. The protein passes through the phospholipid bilayer four times, leaving its C- and N-terminals exposed to the cytoplasm. The C-terminal tail is composed of 50 amino acids and includes post-translational modification sites, as well as binding sites for transcription factors, cytoskeleton elements, and other proteins.
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Many P-type ATPase families are found exclusively in prokaryotes (e.g. Kdp-type K+ uptake ATPases (type III) and all prokaryotic functionally uncharacterized P-type ATPase (FUPA) families), while others are restricted to eukaryotes (e.g. phospholipid flippases and all 13 eukaryotic FUPA families). Horizontal gene transfer has occurred frequently among bacteria and archaea, which have similar distributions of these enzymes, but rarely between most eukaryotic kingdoms, and even more rarely between eukaryotes and prokaryotes.
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Blood 1998; 92:1707-1712 Other possible defects in PS translocation, reported in some patients, require further study.Weiss, HJ: Impaired platelet procoagulant mechanisms in patients with bleeding disorders. Sem. Thromb. Hemost. 35:233-241, 2009 The initially reported patient with Scott Syndrome has been found to have a mutation at a splice-acceptor site of the gene encoding transmembrane protein 16F (TMEM16F).Suzuki J, Umeda M, Sims PJ, Nagata S. Calcium-dependent phospholipid scrambling by TMEM16F.
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Usually it is concentrated at the surface of the membrane, with some degree of penetration. Excited-state relaxation of prodan is sensitive to whether the linkage between phospholipid hydrocarbon tails and the glycerol backbone is of ether or ester type. Therefore, many studies exploited this sensitivity to explore coexisting lipid domains in dual-wavelength ratio measurements, to detect non-bilayer lipid phases, to map membrane structure changes. However, Prodan presence itself is found to change the structure of membaranes.
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ResVax is a nanoparticle-based treatment using a recombinant F lipoprotein or saponin, "extracted from the Quillaja saponaria [or?] Molina bark together with cholesterol and phospholipid." It is aimed at stimulating resistance to respiratory syncitial virus infection, targeting both adult and infant populations. In January 2020, Novovax was given Fast Track status by the FDA to expedite the review process for NanoFlu, a candidate influenze vaccine undergoing a Phase III clinical trial scheduled for completion by mid-2020.
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Rhomboid family members share a conserved core of six transmembrane helices (TMHs), with the Ser and His residues required to form the catalytic dyad embedded in TMH-4 and TMH-6, respectively. This dyad is found deep below the membrane surface, which indicates that the hydrolysis of peptide bonds occurs within the hydrophobic phospholipid bilayer membrane. As a member of the Parl subfamily, PARL has an additional N-terminal TMH which may form a loop to the catalytic core.
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Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme that is activated by thrombin into activated protein C (APC). Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein thrombomodulin. Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with protein S and a phospholipid as cofactors, degrades FVa and FVIIIa.
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In eucaryotic cells, new phospholipids are manufactured by enzymes bound to the part of the endoplasmic reticulum membrane that faces the cytosol. These enzymes, which use free fatty acids as substrates, deposit all newly made phospholipids into the cytosolic half of the bilayer. To enable the membrane as a whole to grow evenly, half of the new phospholipid molecules then have to be transferred to the opposite monolayer. This transfer is catalyzed by enzymes called flippases.
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In animal cells, membrane fluidity is modulated by the inclusion of the sterol cholesterol. This molecule is present in especially large amounts in the plasma membrane, where it constitutes approximately 20% of the lipids in the membrane by weight. Because cholesterol molecules are short and rigid, they fill the spaces between neighboring phospholipid molecules left by the kinks in their unsaturated hydrocarbon tails. In this way, cholesterol tends to stiffen the bilayer, making it more rigid and less permeable.
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Serine active site-containing protein 1, or Protein SERAC1 is a protein in humans that is encoded by the SERAC1 gene. The protein encoded by this gene is a phosphatidylglycerol remodeling protein found at the interface of mitochondria and endoplasmic reticula, where it mediates phospholipid exchange. The encoded protein plays a major role in mitochondrial function and intracellular cholesterol trafficking. Defects in this gene are a cause of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL).
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Ions cannot passively diffuse through the gastrointestinal tract because the epithelial cell membrane is made up of a phospholipid bilayer. The bilayer is made up of two layers of phospholipids in which the charged hydrophilic heads face outwards and the non-charged hydrophobic fatty acid chains are in the middle of the layer. The uncharged fatty acid chains repel ionized, charged molecules. This means that the ionized molecules cannot pass through the intestinal membrane and be absorbed.
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The transmembrane region of many integral membrane proteins consists of one or more alpha helices. The orientations and interactions of these helices directly affect cell signaling and molecular transport across the bilayer. The hydrophobic environment of the phospholipid tails in turn modulates the position and structure of such domains and thus may influence protein function. Conversely, the bilayer itself can (locally) change the thickness of its hydrocarbon region to interact optimally with hydrophobic regions of a transmembrane protein (a.k.a.
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Several studies of diets supplemented with MFGM and its components, including gangliosides and sphingomyelin, have aimed to address measures of cognitive development in pediatric populations. In some of the studies, MFGM supplementation to infant formula was shown to narrow the gap in cognitive development between breastfed and formula-fed infants. Tanaka et al. (2013) studied the neurobehavioral effects of feeding formula supplemented with sphingomyelin-enriched phospholipid in 24 very low birth weight preterm infants (birth weight <1500 g).
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The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7). As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase has cleaved sialic acid residues from the host cell. After the release of new influenza virus, the host cell dies.
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LqhIT2 toxin possesses two non-interacting binding sites: a high-affinity and low- capacity binding site, as well as a low-affinity and high-capacity binding site. LqhIT2 binds to receptor site 4 of the voltage-gated sodium channel, more specifically to loop D2/D3-S. Additionally, the toxin binds non- specifically to the phospholipid bilayer and thus partitions into the cell membrane. However, this binding occurs ten times more slowly than the binding to receptor site 4.
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She showed that the antiviral drug amantadine inhibits proton conduction by direct occlusion of the channel pore. She determined the cholesterol-binding structure of the M2 protein, which sheds light on how cholesterol mediates M2's membrane scission function. In 2020 she determined the first phospholipid-bound structures of the influenza B M2 protein in both its closed and open states. The 1.5 Å structures gave insight into differences in the activation mechanism of BM2 compared to AM2.
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Structures and localization of the enzymes in the CDP-choline pathway. The CDP-choline pathway, first identified by Eugene Kennedy in 1956, is the predominant mechanism by which mammalian cells synthesize phosphatidylcholine (PC) for incorporation into membranes or lipid-derived signalling molecules. The CDP-choline pathway represents one half of what is known as the Kennedy pathway. The other half is the CDP-ethanolamine pathway which is responsible for the biosynthesis of the phospholipid phosphatidylethanolamine (PE).
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Fig. 3. Components of an influenza virosome In contrast to liposomes, virosomes contain functional viral envelope glycoproteins: influenza virus hemagglutinin (HA) and neuraminidase (NA) intercalated in the phospholipid bilayer membrane. They have a typical mean diameter of 150 nm. Essentially, virosomes represent reconstituted empty influenza virus envelopes, devoid of the nucleocapsid including the genetic material of the source virus.h The unique properties of virosomes partially relate to the presence of biologically active influenza HA in their membrane.
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Thus, anti-annexin A5 antibodies increase phospholipid- dependent coagulation steps. The Lupus anticoagulant antibodies are those that show the closest association with thrombosis, those that target β2glycoprotein 1 have a greater association with thrombosis than those that target prothrombin. Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (>40 GPLU or MPLU). Patients with both Lupus anticoagulant antibodies and moderate/high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone.
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Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbp long and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-amino acid repeats separated by linking sequences of variable lengths.
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General reaction catalyzed by phospholipase C The primary catalyzed reaction of PLC occurs on an insoluble substrate at a lipid-water interface. The residues in the active site are conserved in all PLC isotypes. In animals, PLC selectively catalyzes the hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) on the glycerol side of the phosphodiester bond. There is the formation of a weakly enzyme-bound intermediate, inositol 1,2-cyclic phosphodiester, and release of diacyl glycerol (DAG).
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Complement component 7 is a protein involved in the complement system of the innate immune system. C7 is part of the membrane attack complex (MAC) which creates a hole on pathogen surfaces, leading to cell lysis and death. Its primary task is to bind the C5bC6 complex together. This junction alters the configuration of the protein molecules, exposing a hydrophobic site on C7 that allows the C7 to insert into the phospholipid bilayer of the pathogen.
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These regions and their interactions with the surrounding water have been characterized over the past several decades with x-ray reflectometry, neutron scattering and nuclear magnetic resonance techniques. The first region on either side of the bilayer is the hydrophilic headgroup. This portion of the membrane is completely hydrated and is typically around 0.8-0.9 nm thick. In phospholipid bilayers the phosphate group is located within this hydrated region, approximately 0.5 nm outside the hydrophobic core.
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PAF was discovered by French immunologist Jacques Benveniste in the early 1970s. PAF was the first phospholipid known to have messenger functions. Benveniste made significant contributions in the role and characteristics of PAF and its importance in inflammatory response and mediation. Using lab rats and mice, he found that ionophore A23187 (a mobile ion carrier that allows the passage of Mn2+, Ca2+ and Mg2+ and has antibiotic properties against bacteria and fungi) caused the release of PAF.
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The fatty acid is removed from the sn-2 position of the three-carbon backbone of the phospholipid by phospholipase A2 (PLA2) to produce the intermediate lyso-PC (LPC). An acetyl group is then added by LPC acetyltransferase (LPCAT) to produce PAF. Using the de novo pathway, PAF is produced from 1-O-alkyl-2-acetyl-sn-glycerol (AAG). Fatty acids are joined on the sn-1 position with 1-O-hexadecyl being the best for PAF activity.
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PLCs perform their catalytic function at the plasma membrane where their substrate PIP2 is present. This membrane docking is mediated mostly by lipid-binding domains (e.g. PH domain and C2 domain) that display affinity for different phospholipid components of the plasma membrane. It is important to note that research has also discovered that, in addition to the plasma membrane, PLCs also exist within other sub-cellular regions such as the cytoplasm and nucleus of the cell.
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Negative-sense vRNAs that form the genomes of future viruses, RNA-dependent RNA polymerase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7).
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Apolipoprotein E (ApoE) plays an important role in phospholipid and cholesterol homeostasis. After binding ApoER2, ApoE is taken up into the cell and may remain in the intracellular space, be shipped to the cell surface, or be degraded. ApoE binding leads to the cleavage of ApoER2 into secreted proteins by the actions of the plasma membrane protein gamma secretase. ApoE may be the signalling ligand responsible for ApoER2's role in modulating the JNK signalling pathway.
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The protein encoded by this gene belongs to the ARL (ADP-ribosylation factor-like) family of proteins, which are structurally related to ADP-ribosylation factors (ARFs). ARFs, described as activators of cholera toxin (CT) ADP-ribosyltransferase activity, regulate intracellular vesicular membrane trafficking, and stimulate a phospholipase D (PLD) isoform. Although, ARL proteins were initially thought not to activate CT or PLD, later work showed that they are weak stimulators of PLD and CT in a phospholipid dependent manner.
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Their structure physically resembles a star. At the core of their structure is a multi-functional initiator poly(amidoamine) with 16 or 32 primary amines. Lysine and valine amino acids are polymerized to the N-terminus of the core in order to form either an S16 (16 arm SNAPP) or S32 (32 arm SNAPP). The polymerized peptide chains result in several positively charged primary ammonium cations, which help adhere the negatively charged end of the phospholipid bi-layer.
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MAP kinase is imperative for numerous physiological changes including regulation of cell division and differentiation, thus, down- regulation of this pathway may occur during the presence of too much GHB as found in SSADH deficiency. In 2003, Ren and Mody et al. proved that repeated exposure of GHB to MAP kinase affected myelin expression. This is a critical finding since myelin is the electrical and insulating phospholipid layer that surrounds the axons of many neurons in the brain.
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Droplet Interface Bilayers (DIBs) are phospholipid-encased droplets that form bilayers when they are put into contact. The droplets are surrounded by oil and phospholipids are dispersed in either the water or oil. As a result, the phospholipids spontaneously form a monolayer at each of the oil-water interfaces. DIBs can be formed to create tissue-like material with the ability to form asymmetric bilayers, reconstitute proteins and protein channels or made for use in studying electrophysiology.
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Shallow coastal waters also tend to be warmer, further concentrating the molecules through evaporation. While bubbles made mostly of water tend to burst quickly, oily bubbles are much more stable, lending more time to the particular bubble to perform these crucial experiments. The phospholipid is a good example of a common oily compound prevalent in the prebiotic seas. Both of these options require the presence of a massive amount of chemicals and organic material in order to form cells.
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These studies suggest that reduced PtdIns(3,5)P2 levels, by a yet-to-be identified mechanism, mediate neuronal death. In contrast, MTMR2 phosphatase knockout, which also causes peripheral neuropathy, is accompanied by elevation in PtdIns(3,5)P2. Vaccari I, Dina G, Tronchère H, Kaufman E, Chicanne G, Cerri F, Wrabetz L, Payrastre B, Quattrini A, Weisman LS, Meisler MH, Bolino A. Genetic interaction between MTMR2 and FIG4 phospholipid phosphatases involved in Charcot-Marie-Tooth neuropathies. PLoS Genet.
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Almost all of the gastric mucosal defense mechanisms are stimulated and/or facilitated by prostaglandins (PGs), especially PGE2. These cytoprotective PGs stimulate mucus, bicarbonate, and phospholipid secretion; increase mucosal blood flow; and accelerate epithelial restitution and mucosal healing. They also inhibit mast cell activation, and leukocyte and platelet adherence to the vascular endothelium. Thus, continuous generation of PGE2 by gastric mucosa is crucial for the maintenance of mucosal integrity and protection against ulcerogenic and necrotizing agents.
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The pathogenesis of lipoprotein-X in cholestasis is not totally resolved. Normally, the liver excretes lipoprotein complexes into the bile showing phospholipid and unesterified cholesterol concentrations similar to Lipoprotein-X. The in vitro incubation of these bile lipoproteins with serum or albumin leads to the appearance of Lp-X–like particles. These findings suggest that the reflux of bile into the plasma compartment causes the formation of lipoprotein-X in cholestasis as a result of a physicochemical, nonmetabolic process.
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Fully functional membrane Destroyed membrane ;Phospholipases :Phospholipase is an enzyme that transforms the phospholipid molecule into a lysophospholipid (soap) -> the new molecule attracts and binds fat and ruptures cell membranes. Phospholipase A2 is one specific type of phospholipases found in snake venom. :Snake example: Okinawan habu (Trimeresurus flavoviridis) ;Cardiotoxins / Cytotoxins :Cardiotoxins are components that are specifically toxic to the heart. They bind to particular sites on the surface of muscle cells and cause depolarisation -> the toxin prevents muscle contraction.
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The emulsified formulation was relaunched in 1986 by ICI (now AstraZeneca) under the brand name Diprivan. The currently available preparation is 1% propofol, 10% soybean oil, and 1.2% purified egg phospholipid as an emulsifier, with 2.25% glycerol as a tonicity-adjusting agent, and sodium hydroxide to adjust the pH. Diprivan contains EDTA, a common chelation agent, that also acts alone (bacteriostatically against some bacteria) and synergistically with some other antimicrobial agents. Newer generic formulations contain sodium metabisulfite or benzyl alcohol as antimicrobial agents.
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Neptune Wellness Solutions (originally Neptune Technologies and Bioresources) was founded by Henri Harland and Luc Rainville in 1998. The Canadian biotech company conducted some of the first research on the health benefits of krill oil and the unique, absorption capacity of its “phospholipid” molecular structure and the fats contained within it. Neptune secured a family of patents - for an extraction process as well as composition and method of use. In 2002, the company pioneered the production and extraction of Antarctic krill oil.
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Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P.
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This technique uses a patented Microfluidizer to obtain a greater amount of homogenous suspensions that can create smaller particles than homogenizers. A homogenizer is first used to create a coarse suspension which is then pumped into the microfluidizer under high pressure. The flow is then split into two streams which will react at very high velocities in an interaction chamber until desired particle size is obtained. This technique allows for large scale production of phospholipid liposomes and subsequent material nanoencapsulations.
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PgpB is competitively inhibited by phosphatidylethanolamine (PE), a phospholipid formed from DAG. This is therefore an example of negative feedback regulation. The enzyme active site contains a catalytic triad Asp-211, His-207, and His-163 that establishes a charge relay system. However, this catalytic triad is essential for the dephosphorylation of lysophosphatidic acid, phosphatidic acid, and sphingosine-1-phosphate, but is not essential in its entirety for the enzyme's native substrate, phosphatidylglycerol phosphate; His-207 alone is sufficient to hydrolyze PGP.
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Other effects include reduced coordination, which leads to slurred speech, impaired fine-motor skills, and delayed reaction time. The effects of alcohol on the body's neurochemistry are more difficult to examine than some other drugs. This is because the chemical nature of the substance makes it easy to penetrate into the brain, and it also influences the phospholipid bilayer of neurons. This allows alcohol to have a widespread impact on many normal cell functions and modifies the actions of several neurotransmitter systems.
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Most animal cells consist of only a phospholipid bilayer (plasma membrane) and not a cell wall, therefore shrinking up under such conditions. Plasmolysis only occurs in extreme conditions and rarely occurs in nature. It is induced in the laboratory by immersing cells in strong saline or sugar (sucrose) solutions to cause exosmosis, often using Elodea plants or onion epidermal cells, which have colored cell sap so that the process is clearly visible. Methylene blue can be used to stain plant cells.
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Aqueous solutions of manganese(II) chloride are used in 31P-NMR to determine the size and lamellarity of phospholipid vesicles. When manganese chloride is added to a vesicular solution, Mn2+ paramagnetic ions are released, perturbing the relaxation time of the phospholipids' phosphate groups and broadening the resulting 31P resonance signal. Only phospholipids located in the outermost monolayer exposed to Mn2+ experience this broadening. The effect is negligible for multilamellar vesicles, but for large unilamellar vesicles, a ~50% reduction in signal intensity is observed.
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His introduction of 'spin labels' has led to a deep understanding of such motions, and to extensive applications in many biological systems of great interest. These motions include the rates of translational diffusion of lipids in bilayer membranes as well as the rates of trans membrane phospholipid "flip-flop". In fact nitric oxide free radical "spin labels" provided some of the earliest evidence for the fluidity of biological membranes. His recent research was concerned with the physical chemistry of biological membranes.
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In 2011, Yassin et al., on the basis of 16S rRNA signature nucleotide comparisons, menaquinone and phospholipid compositions, and Christie–Atkins–Munch-Petersen (CAMP) tests, proposed that four species—A. haemolyticum, A. hippocoleae, A. phocae, and A. pluranimalium—should continue to be affiliated with the genus Arcanobacterium, whereas the species A. abortisuis, A. bernardiae, A. bialowiezense, A. bonasi, and A. pyogenes should be reclassified as members of a new genus, Trueperella, as Trueperella abortisuis comb. nov., Trueperella bernardiae comb. nov.
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Transmission electron micrograph of lead citrate stained microvesicles. Black bar is 100 nanometers Microvesicles (ectosomes, or microparticles) are a type of extracellular vesicle (EV) that are released from the cell membrane. In multicellular organisms, microvesicles and other EVs are found both in tissues (in the interstitial space between cells) and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs (30 nm in diameter) or as large as 1000 nm.
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Every living cell is encased in a membrane that separates it from its surroundings. Cellular membranes are composed of a phospholipid matrix and proteins, typically in the form of a bilayer. Phospholipids are derived from glycerol with two of the glycerol hydroxyl (OH) protons replaced by fatty acids as an ester, and the third hydroxyl proton has been replaced with phosphate bonded to another alcohol.Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. .
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The polymer is created from esterification reactions with fatty acids and contains 14 to 16 carbons per polyglycerol moiety. Sucrose monoesters are derived from the esterification of sucrose with a fatty acid ester or a fatty acid and it ideally should have a fatty acyl group ranging from 14 to 18 carbon atoms. Lastly, phospholipid such as lecithin, cephalin, and sphingomyelin can also be used as effective emulsifiers. In addition, some of the emulsifier act as a lubricant during the extrusion process.
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T3 and T4 bind to nuclear receptors (thyroid hormone receptors). T3 and T4, although being lipophilic, are not able to passively diffuse through the phospholipid bilayers of target cells, instead relying on transmembrane iodothyronine transporters. The lipophilicity of T3 and T4 requires their binding to the protein carrier thyroid-binding protein (TBG) (thyroxine-binding globulins, thyroxine binding prealbumins, and albumins) for transport in the blood. The thyroid receptors bind to response elements in gene promoters, thus enabling them to activate or inhibit transcription.
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Human mitochondria contain two distinct isoforms of SdhA (Fp subunits type I and type II), these isoforms are also found in Ascaris suum and Caenorhabditis elegans. The subunits form a membrane-bound cytochrome b complex with six transmembrane helices containing one heme b group and a ubiquinone-binding site. Two phospholipid molecules, one cardiolipin and one phosphatidylethanolamine, are also found in the SdhC and SdhD subunits (not shown in the image). They serve to occupy the hydrophobic space below the heme b.
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Canavan disease is an autosomal recessive degenerative disorder that causes progressive damage to nerve cells in the brain, and is one of the most common degenerative cerebral diseases of infancy. It is caused by a deficiency of the enzyme aminoacylase 2, and is one of a group of genetic diseases referred to as leukodystrophies. It is characterized by degeneration of myelin in the phospholipid layer insulating the axon of a neuron and is associated with a gene located on human chromosome 17.
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The plasma membrane is a phospholipid bilayer membrane that separates the cell from its environment and regulates the transport of molecules and signals into and out of the cell. Embedded in the membrane are proteins that perform the functions of the plasma membrane. The plasma membrane is not a fixed or rigid structure, the molecules that compose the membrane are capable of lateral movement. This movement and the multiple components of the membrane are why it is referred to as a fluid mosaic.
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Most NSAIDs act as nonselective inhibitors of the cyclooxygenase (COX) enzymes, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of reversibility), as opposed to the mechanism of aspirin, which is irreversible inhibition. COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation.
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A milestone discovery in the career of Jean Gruenberg was the identification and the characterization of an atypical inverted cone-shaped phospholipid, originally named lysobisphosphatidic acid (LBPA) and also known as bis(monoacylglycero)phosphate (BMP). Using specific monoclonal antibodies, LBPA/BMP was shown to be enriched in intralumenal vesicles of late endosomes and to regulate the intracellular transport and homeostasis of cholesterol. LBPA/BMP is also directly involved in the formation of intracellular vesicles within multivesicular endosomes and endosome-mimicking liposomes.
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Structure of a chylomicron. ApoA, ApoB, ApoC, ApoE are apolipoproteins; green particles are phospholipids; T is triacylglycerol; C is cholesterol ester. A lipoprotein is a biochemical assembly whose primary purpose is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a Triglyceride and Cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center.
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An early morphological event in both the extrinsic and the intrinsic apoptotic pathways is the surface exposure of the phospholipid phosphatidylserine, about 96% of which normally reside in the cytosolic leaflet of the plasma membrane. Phosphatidylserine is translocated to the exoplasmic leaflet by the activation of scramblases, leading to pro-coagulant properties and providing a phagocytic signal to the macrophages that engulf and clear the apoptotic cells. The involvement of other associated proteins aiding scrambling activity cannot be ruled out.
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The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions.
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Where phosphatidylcholine is the principal phospholipid in animals, phosphatidylethanolamine is the principal one in bacteria. One of the primary roles for phosphatidylethanolamine in bacterial membranes is to spread out the negative charge caused by anionic membrane phospholipids. In the bacterium E. coli, phosphatidylethanolamine play a role in supporting lactose permeases active transport of lactose into the cell, and may play a role in other transport systems as well. Phosphatidylethanolamine plays a role in the assembly of lactose permease and other membrane proteins.
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T-tubules are microscopic tubes that run from the cell surface to deep within the cell. They are continuous with the cell membrane, are composed of the same phospholipid bilayer, and are open at the cell surface to the extracellular fluid that surrounds the cell. T-tubules in cardiac muscle are bigger and wider than those in skeletal muscle, but fewer in number. In the centre of the cell they join together, running into and along the cell as a transverse-axial network.
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Since SP-B has a major role in surfactant biogenesis and spreading of surfactant and lipid layer, any disruption to existence of SP-B results in ineffective respiration and lethal pulmonary conditions at birth. Pathology manifestation in full-term infant resembles characteristics of newborn with Respiratory Distress Syndrome. Imaging of epithelial type II cells with SP-B deficiency shows immature lamellar bodies without tightly packed membranes, but rather with loose and unorganized membranes. The ratio of phospholipid-protein also decreases with abnormal phospholipids.
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The complexity of the logic operations, the decisions and actions, increases with the increased number of nanobots. The team estimated that the computing power in the cockroach can be scaled up to that of an 8-bit computer. DNA is folded into an octahedron and coated with a single bilayer of phospholipid, mimicking the envelope of a virus particle. The DNA nanoparticles, each at about the size of a virion, are able to remain in circulation for hours after injected into mice.
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Specific organismal chemical signatures can be used to detect biomass of more cryptic organisms, such as AM fungi or soil bacteria. Lipids, more specifically phospholipids and neutral lipids, contain fatty acids connected to a glycerol backbone. The fatty acid composition of organisms varies, and the proportions of specific fatty acids can be organism specific. For example, in AM fungi the proportion of the fatty acids, 16:1ω5 and 18:1ω7, in the phospholipid portion account for approximately 58% of total fatty acid composition.
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Phorbol derivatives work primarily by interacting with protein kinase C (PKC), although they can interact with other phospholipid membrane receptors. The esters bind to PKC in a similar way to its natural ligand, diacylglycerol, and activate the kinase. Diacylglycerol is degraded quickly by the body, allowing PKC to be reversibly activated. When phorbol esters bind to the receptor, they are not degraded as efficiently by the body, leading to constitutively active PK. PKC is involved in a number of important cell signaling pathways.
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This enzyme converts a phospholipid in the cell membrane by the name of phosphatidylinositol 4,5-bisphosphate (PIP2), into phosphatidylinositol 3,4,5-triphosphate (PIP3), which, in turn, activates protein kinase B (PKB). Activated PKB facilitates the fusion of GLUT4 containing endosomes with the cell membrane, resulting in an increase in GLUT4 transporters in the plasma membrane. PKB also phosphorylates glycogen synthase kinase (GSK), thereby inactivating this enzyme. This means that its substrate, glycogen synthase (GS), cannot be phosphorylated, and remains dephosphorylated, and therefore active.
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The annexins are a family of calcium-dependent phospholipid- binding proteins. Members of the annexin family contain 4 internal repeat domains, each of which includes a type II calcium-binding site. The calcium- binding sites are required for annexins to aggregate and cooperatively bind anionic phospholipids and extracellular matrix proteins. This gene encodes a divergent member of the annexin protein family in which all four homologous type II calcium-binding sites in the conserved tetrad core contain amino acid substitutions that ablate their function.
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The bacterial proteins are denatured in low pH and become more accessible to the proteases, which are unaffected by the acidic environment. The enzymes are later recycled from the phagolysosome before egestion so they are not wasted. The composition of the phospholipid membrane also changes as the phagosome matures. Fusion may take minutes to hours depending on the contents of the phagosome; FcR or mannose receptor-mediated fusion last less than 30 minutes, but phagosomes containing latex beads may take several hours to fuse with lysosomes.
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Phospholipase C cleaving PIP2 into IP3 and DAG Specific signals can trigger a sudden increase in the cytoplasmic Ca2+ levels to 500–1,000 nM by opening channels in the ER or the plasma membrane. The most common signaling pathway that increases cytoplasmic calcium concentration is the phospholipase C (PLC) pathway. # Many cell surface receptors, including G protein-coupled receptors and receptor tyrosine kinases, activate the PLC enzyme. # PLC uses hydrolysis of the membrane phospholipid PIP2 to form IP3 and diacylglycerol (DAG), two classic secondary messengers.
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The ABHD2 gene is down regulated in the lungs of people with Emphysema. Analysis of ABHD2 deficiency in mice found a decrease in phosphatidylcholine levels. The mice developed emphysema which was attributed to an increase in macrophage infiltration, increased inflammatory cytokine levels, an imbalance of protease/anti-protease, and an increase in cell death. This research suggests that ABHD2 is important in maintaining the structural integrity of the lungs, and that disruption of phospholipid metabolism in the alveoli may lead to the development of emphysema.
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Plasma Gelsolin is a sticky protein known to bind to a number of peptides and proteins: Actin (see also: Relationships with actin), Apo-H, Aβ, α-Synuclein, Integrin, Tcp-1, Fibronectin, Syntaxin-4, Tropomyosin, fatty acids and phospholipids (see also: Binding and inactivation of diverse inflammatory mediators): LPA, LPS (endotoxin), LTA, PAF, S1P, polyphosphoinositides including PIP2; and nucleic acids: Ap3A, ATP, ADP. PIP2, a phospholipid component of cell membranes, competes with ATP and actin for pGSN binding, and will dissociate F-Actin-capped pGSN.
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The middle structure is a triglyceride composed of oleoyl, stearoyl, and palmitoyl chains attached to a glycerol backbone. At the bottom is the common phospholipid phosphatidylcholine. In biology and biochemistry, a lipid is a macrobiomolecule that is soluble in nonpolar solvents. Non-polar solvents are typically hydrocarbons used to dissolve other naturally occurring hydrocarbon lipid molecules that do not (or do not easily) dissolve in water, including fatty acids, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E, and K), monoglycerides, diglycerides, triglycerides, and phospholipids.
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Glucose enters the beta cells and goes through glycolysis to form ATP that eventually causes depolarization of the beta cell membrane (as explained in Insulin secretion section of this article). The depolarization process causes voltage-controlled calcium channels (Ca2+) opening, allowing the calcium to flow into the cells. An increased calcium level activates phospholipase C, which cleaves the membrane phospholipid phosphatidylinositol 4,5-bisphosphate into Inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds to receptor proteins in the membrane of the endoplasmic reticulum (ER).
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The CHKB gene encodes for a key protein in phospholipid biosynthesis. The choline kinase (CK) and ethanolamine kinase (EK) proteins, which are coded by the CHKB gene, catalyze the phosphorylation of choline/ethanolamine in vitro to phosphocholine/phosphoethanolamine. The catalysis is controlled by ATP in the presence of magnesium and ADP, and commits choline to the enzymatic pathway for biosynthesis of phosphatidylcholine. This is the first step in the biosynthesis of phosphocholine/phosphoethanolamine in all animal cells, and is done by the Kennedy pathway.
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The plasma membrane or bacterial cytoplasmic membrane is composed of a phospholipid bilayer and thus has all of the general functions of a cell membrane such as acting as a permeability barrier for most molecules and serving as the location for the transport of molecules into the cell. In addition to these functions, prokaryotic membranes also function in energy conservation as the location about which a proton motive force is generated. Unlike eukaryotes, bacterial membranes (with some exceptions e.g. Mycoplasma and methanotrophs) generally do not contain sterols.
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It was first proposed by Otto Heinrich Warburg that cancer originated from irreversible injury to mitochondrial respiration, but the structural basis for this injury has remained elusive. Since cardiolipin is an important phospholipid found almost exclusively in the inner mitochondrial membrane and very essential in maintaining mitochondrial function, it is suggested that abnormalities in CL can impair mitochondrial function and bioenergetics. A study published in 2008 on mouse brain tumors supporting Warburg's cancer theory shows major abnormalities in CL content or composition in all tumors.
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A typical plant cell may have between 103 and 105 plasmodesmata connecting it with adjacent cells equating to between 1 and 10 per µm2. Plasmodesmata are approximately 50–60 nm in diameter at the midpoint and are constructed of three main layers, the plasma membrane, the cytoplasmic sleeve, and the desmotubule. They can transverse cell walls that are up to 90 nm thick. The plasma membrane portion of the plasmodesma is a continuous extension of the cell membrane or plasmalemma and has a similar phospholipid bilayer structure.
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Unlike LAM and its paralogs except GRAMD2B, GRAMD2A lacks a VASt domain. The protein localizes to sites where membranes from different organelles are in close apposition. There, it tethers the endoplasmic reticulum to the plasma membrane through its GRAM domain binding phosphatidylinositol 4,5-bisphosphate in the plasma membrane at sites enriched for the phospholipid. The protein ensures proper stromal interaction molecule 1 (STIM1) recruitment to these sites of membrane contact as part of the store-operated calcium entry pathway – a component of intracellular calcium homeostasis.
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Phorbol esters can directly stimulate PKC. The N-terminal region of PKC, known as C1, binds PMA and DAG in a phospholipid and zinc-dependent fashion. The C1 region contains one or two copies of a cysteine-rich domain, which is about 50 amino-acid residues long, and which is essential for DAG/PMA-binding. The DAG/PMA-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.
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The platelet-activating factor receptor is a G-protein coupled receptor which binds platelet-activating factor. The PAF receptor shows structural characteristics of the rhodopsin (MIM 180380) gene family and binds platelet- activating factor (PAF). PAF is a phospholipid (1-0-alkyl-2-acetyl-sn- glycero-3-phosphorylcholine) that has been implicated as a mediator in diverse pathologic processes, such as allergy, asthma, septic shock, arterial thrombosis, and inflammatory processes.[supplied by OMIM] Its pathogenetic role in chronic kidney failure has also been reported recently.
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Ecarin activates prothrombin through a specific proteolytic cleavage, which produces meizothrombin, a prothrombin-thrombin intermediate which retains the full molecular weight of prothrombin, but possesses a low level of procoagulant enzymatic activity. Crucially, this activity is inhibited by hirudin and other direct thrombin inhibitors, but not by heparin. The ECT is also unaffected by prior treatment with warfarin or the presence of phospholipid-dependent anticoagulants, such as lupus anticoagulant. Thus, the ECT is prolonged in a specific and linear fashion with increasing concentrations of hirudin.
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Simplified structure of a mitochondrion Mitochondria are organelles found in all but one eukaryote. Mitochondria provide energy to the eukaryote cell by converting sugars into ATP. They have two surrounding membranes, each a phospholipid bi-layer; the inner of which is folded into invaginations called cristae where aerobic respiration takes place. The outer mitochondrial membrane is freely permeable and allows almost anything to enter into the intermembrane space while the inner mitochondrial membrane is semi permeable so allows only some required things into the mitochondrial matrix.
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Commercial Brewster angle microscope. Complex phospholipid layer in liquid condensed phase in a Langmuir Trough, imaged by a Brewster angle microscope. A Brewster angle microscope (BAM) is a microscope for studying thin films on liquid surfaces, most typically Langmuir films. In a Brewster angle microscope, both the microscope and a polarized light source are aimed towards a liquid surface at that liquid's Brewster angle, in such a way for the microscope to catch an image of any light reflected from the light source via the liquid surface.
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Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly enhanced by binding to activated Factor V (Va), termed the prothrombinase complex. Prothrombin is produced in the liver and is co-translationally modified in a vitamin K-dependent reaction that converts 10-12 glutamic acids in the N terminus of the molecule to gamma-carboxyglutamic acid (Gla). In the presence of calcium, the Gla residues promote the binding of prothrombin to phospholipid bilayers.
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380x380px PLC cleaves the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Thus PLC has a profound impact on the depletion of PIP2, which acts as a membrane anchor or allosteric regulator. PIP2 also acts as the substrate for synthesis of the rarer lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3), which is responsible for signaling in multiple reactions. Therefore, PIP2 depletion by the PLC reaction is critical to the regulation of local PIP3 concentrations both in the plasma membrane and the nuclear membrane.
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The enzymatic activity of scramblase depends on the calcium concentration present inside the cell. The calcium concentration inside cells is, under normal conditions, very low; therefore, scramblase has a low activity under resting conditions. Phospholipid redistribution is triggered by increased cytosolic calcium and seems to be scramblase-dependent, resulting in a symmetric distribution of negatively charged phospholipids between both leaflets of the lipid bilayer. All scramblases contain an EF hand-like Ca2+binding domain that is probably responsible for the calcium activation of the enzyme.
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The second major phase of Hiskey's research program concerned the role of protein-bound X-Carboxyglutamic (GLA) residues in blood clot formation. He developed a method for chemical modification of the GLA residues in 1982 and studied it using various metal ims and prothrombin fragments binding to phospholipid surfaces. These studies were recognized in Hiskey's National Heart, Lung and Blood Institute's Merit Award for the period 1986 to 1996. The study was extended to include various models containing tris-phosphates and peptides containing several GLA residues.
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The class IA phospholipid kinase, PI-3 kinase, is activated by the majority of RTKs. Similarly to other SH2 domain-containing proteins, PI-3 kinase forms a complex with PY sites on activated receptors. The main function of PI3K activation is the generation of PIP3, which functions as a second messenger to activate downstream tyrosine kinases Btk and Itk, the Ser/Thr kinases PDK1 and Akt (PKB). The major biological functions of Akt activation can be classified into three categories – survival, proliferation and cell growth.
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Pafase, also known as rPAF-AH, was developed to treat severe sepsis. Pafase is the recombinant form of platelet-activating factor acetylhydrolase (PAF-AH, also known as lipoprotein- associated phospholipase A2), an enzyme made naturally by macrophages and found in human blood. PAF-AH inactivates platelet-activating factor, a phospholipid that plays a role in the inflammation seen in sepsis. The enzyme was discovered in the mid-1980s by graduate student Diana Stafforini and researchers Steve Prescott, Guy Zimmerman, and Tom McIntyre at the University of Utah.
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The PLA2G6 gene encodes for a phospholipase A2 enzyme, which is a subclass of enzyme that catalyzes the release of fatty acids from phospholipids. This type of enzyme is responsible for breaking down (metabolizing) phospholipids. Phospholipid metabolism is essential for many body processes, including helping to maintain the integrity of the cell membrane. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.
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Annexin IV (ANX4) belongs to the annexin family of calcium- dependent phospholipid binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. ANX4 has 45 to 59% identity with other members of its family and shares a similar size and exon-intron organization. Isolated from human placenta, ANX4 encodes a protein that has possible interactions with ATP, and has in vitro anticoagulant activity and also inhibits phospholipase A2 activity.
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Familial cases of SP-C dysfunction are inherited in an autosomal dominant pattern, although the onset and severity of lung disease are highly variable, even within the same family. More than 40 distinct mutation variations in SFTPC gene have also been described in patients. Wild-type SP-C proteins are embedded inside the phospholipid bilayer of epithelial type II cell and function to generate and maintain monolayer of surfactant on alveolar surface. Individuals with mutated SFTPC genes tend to manifest lung diseases in late childhood or adulthood.
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An algorithm has been developed to accurately predict time since death with an accuracy of within two days. Techniques for analyzing the necrobiome have now been coupled with forensic entomology, such as phospholipid fatty acid (PLFA) analysis, total soil fatty acid methyl esters, and DNA profiling. Pig carcasses have also become a tool to understand human microbiology, minimizing the issue of variation that exists when using human cadavers as study subjects. This technology is used to simplify the sample collection into sequences that scientists can read.
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Rubber particles are formed in the cytoplasm of specialized latex-producing cells called laticifers within rubber plants. Rubber particles are surrounded by a single phospholipid membrane with hydrophobic tails pointed inward. The membrane allows biosynthetic proteins to be sequestered at the surface of the growing rubber particle, which allows new monomeric units to be added from outside the biomembrane, but within the lacticifer. The rubber particle is an enzymatically active entity that contains three layers of material, the rubber particle, a biomembrane and free monomeric units.
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As the membrane of the phagosome is formed by the fusion of the plasma membrane, the basic composition of the phospholipid bilayer is the same. Endosomes and lysosomes then fuse with the phagosome to contribute to the membrane, especially when the engulfed particle is very big, such as a parasite. They also deliver various membrane proteins to the phagosome and modify the organelle structure. Phagosomes can engulf artificial low-density latex beads and then purified along a sucrose concentration gradient, allowing the structure and composition to be studied.
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Together with bactericidal permeability-increasing protein (BPI), the encoded protein binds LPS and interacts with the CD14 receptor, probably playing a role in regulating LPS-dependent monocyte responses. Studies in mice suggest that the encoded protein is necessary for the rapid acute-phase response to LPS but not for the clearance of LPS from circulation. This protein is part of a family of structurally and functionally related proteins, including BPI, plasma cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). Finally, this gene is found on chromosome 20, immediately downstream of the BPI gene.
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Trophosome tissue development happens by stem cells in the center of each lobule, contributing to new lobules as well as the regeneration of bacteriocytes circulating from the center to the periphery of each lobule through which apoptosis happens. The trophosome tissue thus not only shows high levels of proliferation but also fairly small levels of apoptosis. Furthermore, symbionts in the periphery are constantly digested and replaced by separating symbionts in the middle. Lysophosphatidylethanolamines and free fatty acids are the products of phospholipid hydrolysis by phospholipases through the normal degradation of the membranes.
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DPPC is the main phospholipid of pulmonary surfactant, and it is surface-active due to its amphipathic behaviour and its adsorption capacity. However, adsorption is not optimal at human body temperature for DPPC alone, because at 37 °C it is found in a gel phase. The presence of some unsaturated phospholipids (such as dioleoylphosphatidylcholine [DOPC] or phosphatidylglycerol) and cholesterol increases the surfactant's fluidity, so it can adsorb oxygen more efficiently. When this mixture contacts water, for example, it accumulates at the water-air interface and forms a thin superficial pellicule of surfactant.
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OsO4 is a widely used staining agent used in transmission electron microscopy (TEM) to provide contrast to the image. As a lipid stain, it is also useful in scanning electron microscopy (SEM) as an alternative to sputter coating. It embeds a heavy metal directly into cell membranes, creating a high electron scattering rate without the need for coating the membrane with a layer of metal, which can obscure details of the cell membrane. In the staining of the plasma membrane, osmium(VIII) oxide binds phospholipid head regions, thus creating contrast with the neighbouring protoplasm (cytoplasm).
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These top-down approaches have limitations for the understanding of fundamental molecular regulation, since the host organisms have a complex and incompletely defined molecular composition. In 2019 a complete computational model of all pathways in Mycoplasma Syn3.0 cell was published, representing the first complete in silico model for a living minimal organism. A bottom-up approach to build an artificial cell would involve creating a protocell de novo, entirely from non-living materials. It is proposed to create a phospholipid bilayer vesicle with DNA capable of self- reproducing using synthetic genetic information.
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Phosphatidylserine (PS) is the major acidic phospholipid class that accounts for 13–15 % of the phospholipids in the human cerebral cortex [1]. In the plasma membrane, PS is localized exclusively in the cytoplasmic leaflet where it forms part of protein docking sites necessary for the activation of several key signaling pathways. These include the Akt, protein kinase C (PKC) and Raf-1 signaling that is known to stimulate neuronal survival, neurite growth, and synaptogenesis [2–7]. Modulation of the PS level in the plasma membrane of neurons has a significant impact on these signaling processes.
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SUMO proteins have the widest variety of cellular protein targets after ubiquitin and are involved in processes including transcription, DNA repair, and the cellular stress response. NEDD8 is best known for its role in regulating cullin proteins, which in turn regulate ubiquitin-mediated protein degradation, though it likely also has other functions. Two UBLs, ATG8 and ATG12, are involved in the process of autophagy; both are unusual in that ATG12 has only two known protein substrates and ATG8 is conjugated not to a protein but to a phospholipid, phosphatidylethanolamine.
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An example of a phosphatidylcholine, a type of phospholipid in lecithin. Shown in – choline and phosphate group; – glycerol; – monounsaturated fatty acid; – saturated fatty acid. Lecithin (, from the Greek lekithos "yolk") is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic – they attract both water and fatty substances (and so are both hydrophilic and lipophilic), and are used for smoothing food textures, emulsifying, homogenizing liquid mixtures, and repelling sticking materials. Lecithins are mixtures of glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and phosphatidic acid.
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Recently (+)-totarol was also hypothesized to inhibit gram-positive and acid-fast bacteria via inhibition of FtsZ protein, which forms the Z-ring, a polymer necessary for efficient bacterial cell cytokinesis.Jaiswal, R.; Beuria, T. K.; Mohan, R.; Mahajan, S. K.; Panda, D. Biochemistry. 2007, 46, 4211-4220. (+)-Totarol may also function by disrupting the structural integrity of the phospholipid bilayer of bacteria by weakening Van der Waals interactions with its phenolic group,Micol, V.; Mateo, C. R.; Shapiro, S.; Aranda, F. J.; Villalain, J. Biochim. Biophys. Acta-Biomembranes.
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CASS4 signaling may contribute to platelet activation and aggregation. A PKA/PKG phosphorylation site has been identified in CASS4 on residue S305 in the unstructured domain containing SH2-binding motifs; the functional significance of this phosphorylation is currently unknown. Significantly increased phosphorylation on S249 of CASS4, also in the unstructured domain, after platelet stimulation with the oxidized phospholipid KODA-PC (9-keto-12-oxo-10-dodecenoic acid ester of 2-lyso-phosphocholine, a CD36 receptor agonist) versus thrombin treatment, which may implicate CASS4 mediated signaling in platelet hyperreactivity.
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Rats fed DHA-containing oils experienced marked disruptions to their antioxidant systems, and accumulated significant amounts of phospholipid hydroperoxide in their blood, livers and kidneys. Rabbits fed atherogenic diets containing various oils were found to undergo the greatest amount of oxidative susceptibility of LDL via polyunsaturated oils. In another study, rabbits fed heated soybean oil "grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated." However, Fred Kummerow claims that it is not dietary cholesterol, but oxysterols, or oxidized cholesterols, from fried foods and smoking, that are the culprit.
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Lipid droplets are composed of a neutral lipid core consisting mainly of triacylglycerols (TAGs) and cholesteryl esters surrounded by a phospholipid monolayer. The surface of lipid droplets is decorated by a number of proteins which are involved in the regulation of lipid metabolism. The first and best-characterized family of lipid droplet coat proteins is the perilipin protein family, consisting of five proteins. These include perilipin 1 (PLIN1), perilipin 2 (PLIN2/ ADRP), perilipin 3 (PLIN3/ TIP47), perilipin 4 (PLIN4/ S3-12) and perilipin 5 (PLIN5/ OXPAT/ LSDP5/ MLDP).
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The granule is the defining characteristic of the endoplasm, as they are typically not present within the ectoplasm. These offshoots of the endomembrane system are enclosed by a phospholipid bilayer and can fuse with other organelles as well as the plasma membrane. Their membrane is only semipermeable and allows them to house substances that could be harmful to the cell if they were allowed to flow freely within the cytosol. These granules give the cell a large amount of regulation and control over the wide variety of metabolic activities that take place within the endoplasm.
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AE1 in human red blood cells has been shown to transport a variety of inorganic and organic anions. Divalent anions may be symported with H+. Additionally, it catalyzes flipping of several anionic amphipathic molecules such as sodium dodecyl sulfate (SDS) and phosphatidic acid from one monolayer of the phospholipid bilayer to the other monolayer. The rate of flipping is sufficiently rapid to suggest that this AE1-catalyzed process is physiologically important in red blood cells and possibly in other animal tissues as well. Anionic phospholipids and fatty acids are likely to be natural substrates.
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Palmitoyl-oleyl-sn- phosphatidylcholine, a phosphatidylcholine. This phospholipid is composed of a choline head group and glycerophosphoric acid, with a variety of fatty acids. Usually, one is a saturated fatty acid (in the given figure, this is palmitic acid (hexadecanoic acid, H3C-(CH2)14-COOH); margaric acid (heptadecanoic acid, H3C-(CH2)15-COOH), identified by Gobley in egg yolk, also belong to that class); and the other is an unsaturated fatty acid (here oleic acid, or 9Z-octadecenoic acid, as in Gobley's original egg yolk lecithin). However, there are also examples of disaturated species.
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The cell membrane of nearly all organisms is primarily made up of a phospholipid bilayer, a micelle of hydrophobic fatty acid esters with polar, hydrophilic phosphate "head" groups. Membranes contain additional components, some of which can participate in acid-base reactions. In humans and many other animals, hydrochloric acid is a part of the gastric acid secreted within the stomach to help hydrolyze proteins and polysaccharides, as well as converting the inactive pro-enzyme, pepsinogen into the enzyme, pepsin. Some organisms produce acids for defense; for example, ants produce formic acid.
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ABCB4 gene has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, ABCB4 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression. Other conditions that have been associated with mutations in this gene include low phospholipid associated cholelithiasis syndrome, high gamma glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy and adult biliary fibrosis.Sticova E, Jirsa M (2019) ABCB4 disease: Many faces of one gene deficiency.
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Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum.
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The benefits of virosomes are that the specific structure and small size help with the precision of target cells. The phospholipid membrane prevents the virosome from adverse reactions in the body and the membrane allows the virosome to be biocompatible and biodegradable in the body. The challenges of virosomes is the rapid detection and activation of the immune response against the viral glycoproteins, which can result in a decrease of the virosomes. However, glycoproteins can still induce a prophylactic response against the virus, which helps with establishing virosomes as vaccine delivery systems.
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Arachidonic acid (arachidonic's) has 20 carbons, is present in animal visceral fat (brain, liver, kidney, lung, spleen), and is a 5,8,11,14-tetra- unsaturated fatty acid. I caused by the decomposition of cell membrane in the phospholipid. Prostaglandin, and important as starting materials for the thromboxane, leukotriene such as are known as a series of metabolic pathway to give eicosanoids, arachidonic acid cascade are compounds. C19H31CO2H, IUPAC organization name (5Z , 8Z , 11 Z , 14Z)-icosa-5,8,11,14-tetraenoic acid, numerical representation 20: 4 (5,8,11,14), n-6, molecular weight 304.47, boiling point 169- 171 °C.
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In enzymology, a phosphatidylcholine---sterol O-acyltransferase () is an enzyme that catalyzes the chemical reaction :phosphatidylcholine + a sterol \rightleftharpoons 1-acylglycerophosphocholine + a sterol ester Thus, the two substrates of this enzyme are phosphatidylcholine and sterol, whereas its two products are 1-acylglycerophosphocholine and sterol ester. This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is phosphatidylcholine:sterol O-acyltransferase. Other names in common use include lecithin---cholesterol acyltransferase, phospholipid--- cholesterol acyltransferase, LCAT (lecithin-cholesterol acyltransferase), lecithin:cholesterol acyltransferase, and lysolecithin acyltransferase.
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The word liposome derives from two Greek words: lipo ("fat") and soma ("body"); it is so named because its composition is primarily of phospholipid. Liposomes were first described by British haematologist Alec D Bangham in 1961 (published 1964), at the Babraham Institute, in Cambridge. They were discovered when Bangham and R. W. Horne were testing the institute's new electron microscope by adding negative stain to dry phospholipids. The resemblance to the plasmalemma was obvious, and the microscope pictures served as the first evidence for the cell membrane being a bilayer lipid structure.
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An example of a biological semi- permeable membrane is the lipid bilayer, on which is based on the plasma membrane that surrounds all biological cells. A group of phospholipids (consisting of a phosphate head and two fatty acid tails) arranged into a double layer, the phospholipid bilayer is a semipermeable membrane that is very specific in its permeability. The hydrophilic phosphate heads are in the outside layer and exposed to the water content outside and within the cell. The hydrophobic tails are the layer hidden in the inside of the membrane.
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The prothrombinase complex consists of the serine protease, Factor Xa, and the protein cofactor, Factor Va. The complex assembles on negatively charged phospholipid membranes in the presence of calcium ions. The prothrombinase complex catalyzes the conversion of prothrombin (Factor II), an inactive zymogen, to thrombin (Factor IIa), an active serine protease. The activation of thrombin is a critical reaction in the coagulation cascade, which functions to regulate hemostasis in the body. To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg271 and the other after Arg320.
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Jean Gruenberg (born May 13, 1950) is a Swiss biologist, and a professor at the University of Geneva. His research in the fields of cell biology and biochemistry has significantly contributed to a better understanding of the molecular mechanisms involved in the intracellular traffic within eukaryotic cells, more especially in the endolysosomal pathway. Using innovative approaches such as phospholipid-specific antibodies and reconstituted cell- free systems, Jean Gruenberg and his colleagues were able to unravel several important mechanisms regulating the biogenesis and membrane dynamics of early and late endosomal compartments.
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It is produced by expression in Chinese hamster ovary (CHO) cells. The three epitopes of hepatitis B surface antigen: S, Pre-S1 , and Pre-S2 in their glycosylated and non-glycosylated forms, are displayed on a phospholipid matrix adjuvanted by aluminum hydroxide. This is considered to be direct competitor to Engerix-B manufactured by GlaxoSmithKline, which consists of Hepatitis B surface antigen adsorbed to aluminum hydroxide. The first VLP vaccine that addresses malaria, Mosquirix, (RTS,S) has been approved by regulators in the EU. It was expressed in yeast.
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Upon activation (in platelets) or injury (in erythrocytes, platelets, endothelium, and other cells), certain cells expose the phospholipid phosphatidylserine on their surface and act as catalysts to induce the coagulation cascade. Surface exposure of phosphatidylserine is thought to be brought about by the activation of scramblases. Several enzyme complexes of blood coagulation cascade such as tenase and prothrombinase are activated by the cell surface exposure of the phosphatidylserine. However, the most studied member of the scramblase family PLSCR1 was shown to be defective in translocation of phospholipids when reconstituted into proteoliposomes in vitro.
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Beta-chimaerin is a protein that in humans is encoded by the CHN2 gene. This gene is a member of the chimerin family and encodes a protein with a phorbol- ester/DAG-type zinc finger, a Rho-GAP domain and an SH2 domain. This protein has GTPase-activating protein activity that is regulated by phospholipid binding and binding of diacylglycerol (DAG) induces translocation of the protein from the cytosol to the Golgi apparatus membrane. The protein plays a role in the proliferation and migration of smooth muscle cells.
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The ATG12-ATG5:ATG16L complex is responsible for elongation of the phagophore in the autophagy pathway. ATG12 is first activated by ATG7, proceeded by the conjugation of ATG5 to the complex by ATG10 via a ubiquitination-like enzymatic process. The ATG12-ATG5 then forms a homo-oligomeric complex with ATG16L. With the help of ATG7 and ATG3, the ATG12-ATG5:ATG16L complex conjugates the C terminus of LC3-I to phosphatidylethanolamine in the phospholipid bilayer, allowing LC3 to associate with the membranes of the phagophore, becoming LC3-II.
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By this route, drugs cross the skin by directly passing through both the phospholipids membranes and the cytoplasm of the dead keratinocytes that constitute the stratum corneum. Although this is the path of shortest distance, the drugs encounter significant resistance to permeation. This resistance is caused because the drugs must cross the lipophilic membrane of each cell, then the hydrophilic cellular contents containing keratin, and then the phospholipid bilayer of the cell one more time. This series of steps is repeated numerous times to traverse the full thickness of the stratum corneum.
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The fluid property of functional biological membranes had been determined through labeling experiments, x-ray diffraction, and calorimetry. These studies showed that integral membrane proteins diffuse at rates affected by the viscosity of the lipid bilayer in which they were embedded, and demonstrated that the molecules within the cell membrane are dynamic rather than static. Previous models of biological membranes included the Robertson Unit Membrane Model and the Davidson-Danielli Tri-Layer model. These models had proteins present as sheets neighboring a lipid layer, rather than incorporated into the phospholipid bilayer.
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During the decade of 1970, it was acknowledged that individual lipid molecules undergo free lateral diffusion within each of the layers of the lipid membrane. Diffusion occurs at a high speed, with an average lipid molecule diffusing ~2 µm, approximately the length of a large bacterial cell, in about 1 second. It has also been observed that individual lipid molecules rotate rapidly around their own axis. Moreover, phospholipid molecules can, although they seldom do, migrate from one side of the lipid bilayer to the other (a process known as flip-flop).
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In addition, this specificity helps tether the enzyme tightly to the plasma membrane in order to access substrate through ionic interactions between the phosphate groups of PIP2 and charged residues in the PH domain. While the catalytic core does possess a weak affinity for PIP2, the C2 domain has been shown to mediate calcium-dependent phospholipid binding as well. In this model, the PH and C2 domains operate in concert as a "tether and fix" apparatus necessary for processive catalysis by the enzyme. Phospholipase C-delta isoform 1.
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Factor VIII protein consists of six domains: A1-A2-B-A3-C1-C2, and is homologous to factor V. The A domains are homologous to the A domains of the copper-binding protein ceruloplasmin. The C domains belong to the phospholipid-binding discoidin domain family, and the C2 domain mediate membrane binding. Activation of factor VIII to factor VIIIa is done by cleavage and release of the B domain. The protein is now divided to a heavy chain, consisting of the A1-A2 domains, and a light chain, consisting of the A3-C1-C2 domains.
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The phospholipid composition of a cell membrane affects the arrangement of cholesterol within the membrane and the ability for CDC to bind and initiate pore-formation. For example, perfringolysin O will preferentially bind to cholesterol-rich membranes composed mainly of phospholipids containing 18-carbon acyl chains. Lipids having a conical molecular shape alter the energetic state of membrane cholesterol, augmenting the interaction of the sterol with the cholesterol-specific cytolysin. Since high cholesterol concentrations are required for CDC binding/pore-formation, it was thought that CDC would associate with lipid rafts.
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Mutations of ABCA3 consist of missense, nonsense, frameshift, splice-cite, insertion or deletion. These mutations are classified into two types of ABCA3 mutations, those that preclude normal trafficking of ABCA3 from ER to lamellar membrane, and those that affect ATP-binding ability of ABCA3 needed for phospholipid transportation. Due to its roles in lamellar body biogenesis and maturation of surfactant proteins, epithelial type II cells with altered ABCA3 exhibit premature lamellar bodies and damaged maturation of SP-B/SP-C. Surfactant samples from patients with ABCA3 deficiency do not lower surface tension as effectively.
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To distinguish them from living cells, apoptotic cells carry specific 'eat me' signals, such as the presence of phosphatidyl serine (resulting from phospholipid flip-flop) or calreticulin on the outer leaflet of the cell membrane. Efferocytosis triggers specific downstream intracellular signal transduction pathways, for example resulting in anti-inflammatory, anti-protease and growth-promoting effects. Conversely, impaired efferocytosis has been linked to autoimmune disease and tissue damage. Efferocytosis results in production by the ingesting cell of mediators such as hepatocyte- and vascular endothelial growth factor, which are thought to promote replacement of the dead cells.
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DHA is the main n-3 fatty acid and can be obtained as DHA itself from dietary sources such as fish and fish oils, or as the DHA precursor linolenic acid. With a high DHA intake, plasma lipid DHA content increases, aiding neurological development, as demonstrated by increases in memory and learning ability. Other benefits of n-3 and DHA include promotion of neurogenesis, increased neuron size and phospholipid synthesis, as well as protection against cell death and peroxidative brain damage by damaging free radicals in the rodent model and presumably across the mammalian kingdom.
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As the protons bind to the subunits of the Fo domains, they cause parts of it to rotate. This rotation is propagated by a 'camshaft' to the F1 domain. ADP and Pi (inorganic phosphate) bind spontaneously to the three β subunits of the F1 domain, so that every time it goes through a 120° rotation ATP is released (rotational catalysis). The Fo domains sits within the membrane, spanning the phospholipid bilayer, while the F1 domain extends into the cytosol of the cell to facilitate the use of newly synthesized ATP.
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Detailed diagram of lipid bilayer cell membrane The cell membrane, or plasma membrane, is a biological membrane that surrounds the cytoplasm of a cell. In animals, the plasma membrane is the outer boundary of the cell, while in plants and prokaryotes it is usually covered by a cell wall. This membrane serves to separate and protect a cell from its surrounding environment and is made mostly from a double layer of phospholipids, which are amphiphilic (partly hydrophobic and partly hydrophilic). Hence, the layer is called a phospholipid bilayer, or sometimes a fluid mosaic membrane.
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The toxicity of ribotoxins results from the combination of their specific catalytic activity and their ability to cross lipid membranes. Since no protein receptor has been found, the lipid composition of these membranes is a determining factor of their cytotoxic activity. Using phospholipid model systems it has been demonstrated that α-sarcin is able to bind to lipid vesicles enriched in acid phospholipids, promoting their aggregation, leading to fusion, and altering their permeability. This allows the protein to be translocated through certain lipid bilayers in absence of any other protein.
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These kinases have key roles in the formation of invadopodia and when activated, phosphorylate multiple proteins involved in invadopodia formation including Tks5, synaptjanin-2, and the Abl-family kinase Arg4. The phosphorylation of these proteins leads to the recruitment of the Neural Wiskott-Aldrich syndrome protein (N-Wasp) to invadopodia, which requires Arp2/3, to activate actin polymerization and thus invadopodia elongation. A key step during invadopodia formation is the stabilization of invadopodia, which involves the interaction of PX domain of Tks5 (a scaffold protein) with phospholipid, PI(3,4)P2 to anchor the invadopodia core to the plasma membrane.
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Ethosomes are mainly composed of multiple, concentric layers of flexible phospholipid bylayers, with a relative high concentration of ethanol (20-45%), glycols and water.Touitou E. Compositions for applying active substances to or through the skin; Patent number: 5540934 Granted 1996Touitou E. Composition for applying active substances to or through the skin; Patent number 5716638 Granted 1998 Their overall structure has been confirmed by 31P-NMR, EM and DSC. They have high penetration of the horny layer of the skin, which enhances the permeation of encapsulated drugs. The mechanism of permeation enhancement is attributed to the overall properties of the system.
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Both the alpha and beta (all trans) isomers of parinaric acid are used as molecular probes of lipid-lipid interactions, by monitoring phase transitions in bilayer lipid membranes. α-Parinaric acid was shown to integrate normally into the phospholipid bilayer of mammalian cells, nervous tissue, with minimal effects on the biophysical properties of the membrane. Molecular interactions with neighboring membrane lipids will affect the fluorescence of α-parinaric acid in predictable ways, and the subsequent subtle changes in energy intensities may be measured spectroscopically. Researchers have put α-parinaric to good use in the study of membrane biophysics.
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Phosphatidylinositol 3-phosphate (PtdIns3P) is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases (PI 3-kinases) activity on phosphatidylinositol. PtdIns3P is dephosphorylated by the myotubularin family of phosphatases, on the D3 position of the inositol ring, and can be converted to PtdIns(3,5)P2 by the lipid kinase PIKfyve. Both FYVE domains and PX domains - found in proteins such as SNX1, HGS, and EEA1 - bind to PtdIns3P.
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Plastic responses to temperature are essential among ectothermic organisms, as all aspects of their physiology are directly dependent on their thermal environment. As such, thermal acclimation entails phenotypic adjustments that are found commonly across taxa, such as changes in the lipid composition of cell membranes. Temperature change influences the fluidity of cell membranes by affecting the motion of the fatty acyl chains of glycerophospholipids. Because maintaining membrane fluidity is critical for cell function, ectotherms adjust the phospholipid composition of their cell membranes such that the strength of van der Waals forces within the membrane is changed, thereby maintaining fluidity across temperatures.
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When PAP is inactive, DGK drives the reaction in reverse, allowing phosphatidate to accumulate as it brings down DAG levels. Phosphatidate can then be converted into an activated form, CDP-DAG, through the liberation of a pyrophosphate from a CTP molecule, or into cardiolipin. CDP-DAG is a principal precursor used by the body in phospholipid synthesis. Furthermore, because both phosphatidate and DAG function as secondary messengers, PAP is able to exert extensive and intricate control of lipid metabolism far beyond its local effect on phopshatidate and DAG concentrations and the resulting effect on the direction of lipid flux as outlined above.
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Like most unsaturated fatty acids, the 9-HODEs formed in cells are incorporated into cellular phospholipids principally at the sn-2 position of the phospholipid (see Phospholipase A2);Exp Dermatol. 1993 Feb;2(1):38-4J Lipid Res. 1993 Sep;34(9):1473-82 since, however, the linoleic acid bound to cellular phospholipids is susceptible to non-enzymatic peroxidation and free- radical attack,Free Radic Biol Med. 1995 Jun;18(6):1003-12Biochim Biophys Acta. 1999 May 18;1438(2):204-12 the 9-HODEs in cellular phospholipids may also derive more directly from in-situ oxidation.
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The asymmetry of the biological membrane reflects the different functions of the two leaflets of the membrane. As seen in the fluid membrane model of the phospholipid bilayer, the outer leaflet and inner leaflet of the membrane are asymmetrical in their composition. Certain proteins and lipids rest only on one surface of the membrane and not the other. • Both the plasma membrane and internal membranes have cytosolic and exoplasmic faces • This orientation is maintained during membrane trafficking – proteins, lipids, glycoconjugates facing the lumen of the ER and Golgi get expressed on the extracellular side of the plasma membrane.
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Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans. ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels. Circulating PL-rich HDL particles have high cholesterol efflux abilities. Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state, likely through activation by Angptl8, a feeding-induced hepatokine, to inhibit postprandial LPL activity in cardiac and skeletal muscles, as suggested by the ANGPTL3-4-8 model.
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Lipid phosphate phosphohydrolase 3 (LPP3), also known as phospholipid phosphatase 3 (PLPP3) and phosphatidic acid phosphatase type 2B (PAP-2b or PPAP2B), is an enzyme that in humans is encoded by the PPAP2B gene on chromosome 1. It is ubiquitously expressed in many tissues and cell types. LPP3 is a cell-surface glycoprotein that hydrolyzes extracellular lysophosphatidic acid (LPA) and short-chain phosphatidic acid. Its function allows it to regulate vascular and embryonic development by inhibiting LPA signaling, which is associated with a wide range of human diseases, including cardiovascular disease and cancer, as well as developmental defects.
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For C. tropicalis to fully enter and cause infection in the host, it needs some helpers. First, once it is attached onto the host tissues, extracellular enzymes called the proteases will be produced to facilitate the penetration of the pathogen and allow it to interfere with the host defense system. proteases will hydrolyze peptide bonds; secreted aspartic proteases (SAP) support C. tropicalis to be attached and penetrate deep into the tissues to affect the organs. phospholipases will hydrolyze phospholipid; assist to break the epithelial cell membrane structure allowing the hyphal tip to enter into the cytoplasm.
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Atrium of the new building at night The emphasis on classical molecular biology shifted towards cell biology and development, so that the Molecular Genetics division was renamed Cell Biology. Mark Bretscher discovered the topological way proteins are arranged in the human erythrocyte membrane and its phospholipid asymmetry. Richard Henderson and Nigel Unwin developed electron crystallography to determine the structure of two-dimensional arrays, applying this to the bacterial purple protein, bacteriorhodopsin. Barbara Pearse discovered the major components of clathrin- coated vesicles, structures formed during endocytosis, and a low resolution structure of the cage-like lattice around them was determined.
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Often prenatal vitamins also have a reduced dosage of vitamins that may be detrimental to the fetus when taken in high doses (such as vitamin A). Many prenatal manufacturers have chosen to include the omega-3 fatty acid, docosahexaenoic acid (DHA) in their product, either as an ingredient in the formula or as a complementary softgel. Although explicitly in many formulas to support neural development, the omega-3 fatty acids are used by both mother and fetus to create the phospholipid bilayer that makes up cell membranes. L-arginine has tentative evidence of benefit in reducing intrauterine growth restriction.
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Annexin A2 also known as annexin II is a protein that in humans is encoded by the ANXA2 gene. Annexin 2 is involved in diverse cellular processes such as cell motility (especially that of the epithelial cells), linkage of membrane- associated protein complexes to the actin cytoskeleton, endocytosis, fibrinolysis, ion channel formation, and cell matrix interactions. It is a calcium-dependent phospholipid-binding protein whose function is to help organize exocytosis of intracellular proteins to the extracellular domain. Annexin II is a pleiotropic protein meaning that its function is dependent on place and time in the body.
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Arcus senilis is a depositing of phospholipid and cholesterol in the peripheral cornea in patients over the age of 60 which appears as a hazy white, grey, or blue opaque ring (peripheral corneal opacity). Arcus is common and benign when it is in elderly patients. However, if arcus appears in patients less than 50 years old, it is termed "arcus juvenilis" and is associated with abnormally high cholesterol in the body with increased risks for cardiovascular disease. Arcus may also present as a white ring, which is visible in front of the periphery of the iris.
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The putative phospholipid-binding site, which is the active site of Tafazzin, is a 57 amino acid cleft with two open ends and positively charged residues. In addition, tafazzin localizes to the membrane leaflets facing the intermembrane space (IMS), which is crucial for remodeling. Tafazzin differs from phospholipases in that it contains a conserved histidine residue, His-77, as part of the conserved HX4D motif seen in acyltransferases. This motif is responsible for facilitating the Asp-His dyad mechanism seen in many serine proteases. Many unique forms of tafazzin have been identified, with lengths from 129 to 292 amino acids.
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A cell membrane defines a boundary between a cell and its environment. The primary constituent of a membrane is a phospholipid bilayer that forms in a water-based environment due to the hydrophilic nature of the lipid head and the hydrophobic nature of the two tails. In addition there are other lipids and proteins in the membrane, the latter typically in the form of isolated rafts. Of the numerous models that have been developed to describe the deformation of cell membranes, a widely accepted model is the fluid mosaic model proposed by Singer and Nicolson in 1972.
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Blood types Red blood cells contain antigens in their plasma membranes that distinguish them as part of a specific category of blood cell. These antigens can be polysaccharides, glycoproteins, or GPI (a glycolipid) -linked proteins. Antigens range in complexity, from small molecules bound to the extracellular side of the phospholipid bilayer, to large membrane proteins that loop many times between both sides of the membrane. The smaller polysaccharide antigens classify blood cells into types A, B, AB, and O, while the larger protein antigens classify blood cells into types Rh D-positive and Rh D-negative.
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A hypothetical cell membrane termed an azotosome capable of functioning in liquid methane in Titan conditions was computer-modeled in an article published in February 2015. Composed of acrylonitrile, a small molecule containing carbon, hydrogen, and nitrogen, it is predicted to have stability and flexibility in liquid methane comparable to that of a phospholipid bilayer (the type of cell membrane possessed by all life on Earth) in liquid water.Life 'not as we know it' possible on Saturn's moon Titan. An analysis of data obtained using the Atacama Large Millimeter / submillimeter Array (ALMA), completed in 2017, confirmed substantial amounts of acrylonitrile in Titan's atmosphere.
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It has also been detected in several bacteria and a chloroplast form is observed in alga and higher plants. Inositol phosphates play an important role in signal transduction. In Saccharomyces cerevisiae (Baker's yeast), the transcriptional regulation of the INO1 gene encoding inositol-3-phosphate synthase has been studied in detail and its expression is sensitive to the availability of phospholipid precursors as well as growth phase. The regulation of the structural gene encoding 1L-myo-inositol-1-phosphate synthase has also been analyzed at the transcriptional level in the aquatic angiosperm, Spirodela polyrrhiza (Giant duckweed) and the halophyte, Mesembryanthemum crystallinum (Common ice plant).
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Platelet-activating factor, also known as PAF, PAF-acether or AGEPC (acetyl- glyceryl-ether-phosphorylcholine), is a potent phospholipid activator and mediator of many leukocyte functions, platelet aggregation and degranulation, inflammation, and anaphylaxis. It is also involved in changes to vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well as augmentation of arachidonic acid metabolism in phagocytes. PAF is produced by a variety of cells, but especially those involved in host defense, such as platelets, endothelial cells, neutrophils, monocytes, and macrophages. PAF is continuously produced by these cells but in low quantities and production is controlled by the activity of PAF acetylhydrolases.
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The presence of cholesterol in the membrane of the target cell is required for CDC pore formation. The arrangement of cholesterol molecules in the bilayer may also be important for successful binding. The non-polar hydrocarbon tail of cholesterol orients itself toward the polar center of the membrane lipid bilayer, while the 3-β-OH group is oriented closer to the ester bonds formed by the fatty acid chains, and glycerol backbones closer to the membrane surface. Even with the 3-β-OH group near the membrane surface, it is not very exposed compared to the phospholipid head groups.
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The availability of cholesterol at the membrane surface is dependent upon its interaction with other membrane components such as phospholipids and proteins; and the more cholesterol interacts with these components the less available it is to interact with extramembranous molecules. Some factors that affect cholesterols availability are size of the polar head groups and the ability of the phospholipid to hydrogen bond with the 3-β-OH group of cholesterol. Cholesterol associates with phospholipids, forming a stoichiometric complex and contributes to membrane fluidity. If cholesterol concentration exceeds a certain point, free cholesterol will begin to precipitate out of the membrane.
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However, surfactant decreases the alveolar surface tension, as seen in cases of premature infants suffering from infant respiratory distress syndrome. The normal surface tension for water is 70 dyn/cm (70 mN/m) and in the lungs it is 25 dyn/cm (25 mN/m); however, at the end of the expiration, compressed surfactant phospholipid molecules decrease the surface tension to very low, near-zero levels. Pulmonary surfactant thus greatly reduces surface tension, increasing compliance allowing the lung to inflate much more easily, thereby reducing the work of breathing. It reduces the pressure difference needed to allow the lung to inflate.
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MAMS play an important role in Ca+2 Homeostasis, phospholipid and cholesterol metabolism. Research has associated the alteration of these functions of MAMs in Alzheimer's disease. Mitochindrial associated membranes associated with Alzheimer's disease have been reported to have an up- regulation of lipids synthesized in the MAMs juxtaposition and an up regulation of protein complexes present in the contact region between the ER and mitochondria. Research has suggested that the sites of MAM are the primary sites of activity for γ-secretase activity and amyloid precursor protein (APP) localization along with the presenilin 1 (PS1), presenilin 2 (PS2) proteins.
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Contrastingly, reversible electroporation occurs when the electricity applied with the electrodes is below the electric field threshold of the target tissue. Because the electricity applied is below the cells' threshold, it allows the cells to repair their phospholipid bilayer and continue on with their normal cell functions. Reversible electroporation is typically done with treatments that involve getting a drug or gene (or other molecule that is not normally permeable to the cell membrane) into the cell. Not all tissue has the same electric field threshold; therefore careful calculations need to be made prior to a treatment to ensure safety and efficacy.
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Several salt-tolerance mechanisms of H. werneckii have been studied on molecular level. For example, it is known that its major compatible solutes are glycerol, erythritol, arabitol, and mannitol; melanin accumulation of the cell wall aids in retention of at least glycerol inside of the cell. Several components of the high osmolarity glycerol (HOG) signalling pathway (which controls responses to osmotic shock) have been studied in detail and some seem to differ in function compared to their counterparts in Saccharomyces cerevisiae. Adaptation to high concentrations of salt are also accompanied by changes in membrane lipid composition, mainly by increasing the unsaturation of the phospholipid fatty acids.
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The MAM is enriched in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face. Because mitochondria are dynamic organelles constantly undergoing fission and fusion events, they require a constant and well-regulated supply of phospholipids for membrane integrity. But mitochondria are not only a destination for the phospholipids they finish synthesis of; rather, this organelle also plays a role in inter-organelle trafficking of the intermediates and products of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, and glycosphingolipid anabolism. Such trafficking capacity depends on the MAM, which has been shown to facilitate transfer of lipid intermediates between organelles.
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However, fatty acids are also important components of the phospholipids that form the phospholipid bilayers out of which all the membranes of the cell are constructed (the cell wall, and the membranes that enclose all the organelles within the cells, such as the nucleus, the mitochondria, endoplasmic reticulum, and the Golgi apparatus). The "uncombined fatty acids" or "free fatty acids" found in the circulation of animals come from the breakdown (or lipolysis) of stored triglycerides. Because they are insoluble in water, these fatty acids are transported bound to plasma albumin. The levels of "free fatty acids" in the blood are limited by the availability of albumin binding sites.
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Chemical structure of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,4)-bisphosphate Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)P2 at the plasma membrane activates a number of important cell signaling pathways. PtdIns(3,4)P2 is dephophosphorylated by the phosphatase INPP4B on the 4 position of the inositol ring and by the TPTE (transmembrane phosphatases with tensin homology) family of phosphatases on the 3 position of the inositol ring. The PH domain in a number of proteins binds to PtdIns(3,4)P2 including the PH domain in PKB.
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In order to adapt to their environment, bacteria alter the phospholipid composition of their membranes. Inhibiting this pathway may thus be a leverage point in disrupting bacterial proliferation. By studying Yersinia pestis, which causes bubonic, pneumonic, and septicaemic plagues, researchers have shown that FabB, FabF, and FabH can theoretically all be inhibited by the same drug due to similarities in their binding sites. However, such a drug has not yet been developed. Cerulenin, a molecule that appears to inhibit by mimicking the “condensation transition state” can only inhibit B or F, but not H. Another molecule, thiolactomycin, which mimics malonyl ACP in the active site, can ony inhibit FabB.
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PA is a unique phospholipid in that it has a small highly charged head group that is very close to the glycerol backbone. PA is known to play roles in both vesicle fission and fusion, and these roles may relate to the biophysical properties of PA. At sites of membrane budding or fusion, the membrane becomes or is highly curved. A major event in the budding of vesicles, such as transport carriers from the Golgi, is the creation and subsequent narrowing of the membrane neck. Studies have suggested that this process may be lipid-driven, and have postulated a central role for DAG due to its, likewise, unique molecular shape.
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This exclusion is based on synthesis-specific channel activation: a recent study found that in the bed nucleus of the stria terminalis, calcium entry through voltage-sensitive calcium channels produced an L-type current resulting in 2-AG production, while activation of mGluR1/5 receptors triggered the synthesis of anandamide. Evidence suggests that the depolarization-induced influx of calcium into the post-synaptic neuron causes the activation of an enzyme called transacylase. This enzyme is suggested to catalyze the first step of endocannabinoid biosynthesis by converting phosphatidylethanolamine, a membrane-resident phospholipid, into N-acyl- phosphatidylethanolamine (NAPE). Experiments have shown that phospholipase D cleaves NAPE to yield anandamide.
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Schematic of how the addition of ethanol induces non-lamellar phases; hexaganol(I) and hexagonal(II) versus the lamellar phase described as the bilayer on top of bilayer. Below the schematic is an example of how the hydrophilic region (head group) can be larger or smaller than the hydrophobic region (acyl chains) which affects the curvature as well as the phase of the phospholipid. When lipids are extracted or isolated from biomembranes, Polymorphism and mesomorphism can occur because they are then no longer under the intermolecular constraints that are present within the biomembrane. This can lead to formation of non-lamellar (non-bilayer) or lamellar phases in phospholipids.
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The simulations also support that the interior of the membrane starts to become more hydrophilic due to the presence of water molecules in the interior region once the membrane is partially destroyed. The presence of ethanol also induced the formation of non-lamellar phases (non-bilayer) within the interior region (hydrophobic cored) of the phospholipid membrane. The results are supported by the simulations which show that at approximately 12 mol% of ethanol the membrane was no longer able to tolerate and adapt to the presence of the ethanol resulting in non-lamellar phases. The formations of the non- lamellar phases are described as being irreversible inverted-micelles.
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First messengers are extracellular factors, often hormones or neurotransmitters, such as epinephrine, growth hormone, and serotonin. Because peptide hormones and neurotransmitters typically are biochemically hydrophilic molecules, these first messengers may not physically cross the phospholipid bilayer to initiate changes within the cell directly—unlike steroid hormones, which usually do. This functional limitation requires the cell to have signal transduction mechanisms to transduce first messenger into second messengers, so that the extracellular signal may be propagated intracellularly. An important feature of the second messenger signaling system is that second messengers may be coupled downstream to multi-cyclic kinase cascades to greatly amplify the strength of the original first messenger signal.
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Since the active sites of each catalytic domain are separated by a distance of 40 Å, they are not believed to allosterically effect one another. In contrast, the linker domain is composed of α helices supplied by the two catalytic domains: each domain contributes five helices from their N termini and one from a helix that spans both the catalytic domain and the linker domain. At the center of the linker domain resides an 8 by 35 Å hydrophobic tunnel with two phospholipids bound at each end. The head of each phospholipid points outward towards solution while the tails are embedded within the enzyme.
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The enzymatic biosynthesis of the N-acyl amide class of metabolites is a topic of active research with various pathways being discovered for specific N-acyl amides. For example, a proposed biosynthetic pathway for the N-acyl ethanolamines (NAEs) has been the hydrolysis of an unusual phospholipid precursor, N-acyl- phosphatidylethanolamine (NAPE), by a phospholipase D activity to liberate NAE and, as a byproduct, phosphatidic acid. Mice deficient in the enzyme NAPE-PLD show decreased in a subset of brain NAEs, providing genetic evidence for this proposal, at least for a subset of the NAEs. Other biosynthetic pathways do exist and are currently being elucidated.
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The trapdoor mechanism is responsible for the opening of ion channels in hair cell. However, more evidence now indicate that the gating of MscL specifically is moderated by the membrane-mediated mechanism, which relies on changes in membrane thickness or curvature that can alter the energetic balance of embedded proteins. This is supported by the observations that variations in the thickness of the phospholipid bilayer or the addition of compounds that induce spontaneous membrane curvature directly impact the tension required to open MscL. Analysis of the lateral pressure profile in the lipid bilayer showed that the interface region between the hydrocarbon and polar head groups produces high tension.
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Proteomics studies have elucidated the association of many other families of proteins to the lipid surface including proteins involved in membrane trafficking, vesicle docking, endocytosis and exocytosis. Analysis of the lipid composition of lipid droplets has revealed the presence of a diverse set of phospholipid species; phosphatidylcholine and phosphatidylethanolamine are the most abundant, followed by phosphatidylinositol. Lipid droplets vary greatly in size, ranging from 20-40 nm to 100 um. In adipocytes, lipid bodies tend to be larger and they may compose the majority of the cell, while in other cells they may only be induced under certain conditions and are considerably smaller in size.
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Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a variety of different bacteria, fungi, animal and plant cells contain aquaporins through which water can flow more rapidly into and out of the cell than by diffusing through the phospholipid bilayer. Aquaporins have six membrane-spanning alpha helical domains with both carboxylic and amino terminals on the cytoplasmic side. Two hydrophobic loops contain conserved asparagine-proline-alanine NPA motif which form a barrel surrounding a central pore-like region that contains additional protein density.
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C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. This C2 domain is about 116 amino-acid residues and is located between the two copies of the C1 domain in Protein Kinase C (that bind phorbol esters and diacylglycerol) (see PDOC00379) and the protein kinase catalytic domain (see PDOC00100). Regions with significant homology to the C2-domain have been found in many proteins. The C2 domain is thought to be involved in calcium-dependent phospholipid binding and in membrane targeting processes such as subcellular localisation.
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Comparison of transport proteins Antiporter illustration An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions, one into the cell and one out of the cell. Na+/H+ antiporters have been reviewed. In secondary active transport, one species of solute moves along its electrochemical gradient, allowing a different species to move against its own electrochemical gradient. This movement is in contrast to primary active transport, in which all solutes are moved against their concentration gradients, fueled by ATP.
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Studies have also shown that the dihedral angle between groups on C-2 and C-3 in CP-99994 is critical for activity of the NK1 receptor antagonists. The bridgehead basic nitrogen is thought to interact with the NK1 receptor by mediating its recognition through ion pair site. It has been found that the basic nitrogen atoms in pyrido[3,4-b]pyridine do have an anchoring function in the phospholipid component of the cell membrane. In the development of MK-869, it was discovered that 3,5-disubstitution of the benzyl ring in the ether series gave greater potency than the 2-methoxy substitution in earlier benzylamine structures.
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When performing non- selective measurements, a sum signal from several analytes is measured which means that multivariate data analyses such as neural networks have to be used for quantification. However, it is also possible to use selectively measuring polymers, so-called molecular imprinted polymers (MIPs) which provide artificial recognition elements. When using biosensors, polymers such as polyethylene glycols or dextrans are applied onto the layer system, and on these recognition elements for biomolecules are immobilized. Basically, any molecule can be used as recognition element (proteins such as antibodies, DNA/RNA such as aptamers, small organic molecules such as estrone, but also lipids such as phospholipid membranes).
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Compared metavinculin sequences from pig, man, chicken, and frog, and found the insert to be bipartite: the first part variable and the second highly conserved. Both vinculin isoforms co-localize in muscular adhesive structures, such as dense plaques in smooth muscles, intercalated discs in cardiomyocytes, and costameres in skeletal muscles. Metavinculin tail domain has a lower affinity for the head as compared with the vinculin tail. In case of metavinculin, unfurling of the C-terminal hydrophobic hairpin loop of tail domain is impaired by the negative charges of the 68-amino acid insert, thus requiring phospholipid-activated regular isoform of vinculin to fully activate the metavinculin molecule.
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It is important to note that certain factors have far-reaching effects on the percentage of liposome that are yielded in manufacturing, as well as the actual amount of realized liposome entrapment and the actual quality and long-term stability of the liposomes themselves. They are the following: (1) The actual manufacturing method and preparation of the liposomes themselves; (2) The constitution, quality, and type of raw phospholipid used in the formulation and manufacturing of the liposomes; (3) The ability to create homogeneous liposome particle sizes that are stable and hold their encapsulated payload. These are the primary elements in developing effective liposome carriers for use in dietary and nutritional supplements.
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Individual PH domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring, e.g., some bind phosphatidylinositol (4,5)-bisphosphate but not phosphatidylinositol (3,4,5)-trisphosphate or phosphatidylinositol (3,4)-bisphosphate, while others may possess the requisite affinity. This is important because it makes the recruitment of different PH domain containing proteins sensitive to the activities of enzymes that either phosphorylate or dephosphorylate these sites on the inositol ring, such as phosphoinositide 3-kinase or PTEN, respectively. Thus, such enzymes exert a part of their effect on cell function by modulating the localization of downstream signaling proteins that possess PH domains that are capable of binding their phospholipid products.
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The sequences of amino acids of motilin is: Phe-Val-Pro-Ile-Phe- Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly-Gln. The structure and dynamics of the gastrointestinal peptide hormone motilin have been studied in the presence of isotropic q = 0.5 phospholipid bicelles. The NMR solution structure of the peptide in acidic bicelle solution was determined from 203 NOE-derived distance constraints and six backbone torsion angle constraints. Dynamic properties for the 13Cα→1H vector in Leu-10 were determined for motilin specifically labeled with 13C at this position by analysis of multiple-field relaxation data.
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T-tubules are tubules formed from the same phospholipid bilayer as the surface membrane or sarcolemma of skeletal or cardiac muscle cells. They connect directly with the sarcolemma at one end before travelling deep within the cell, forming a network of tubules with sections running both perpendicular (transverse) to and parallel (axially) to the sarcolemma. Due to this complex orientation, some refer to T-tubules as the transverse-axial tubular system. The inside or lumen of the T-tubule is open at the cell surface, meaning that the T-tubule is filled with fluid containing the same constituents as the solution that surrounds the cell (the extracellular fluid).
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The X-ray crystallographic structure of potato PSI, recombinantly expressed separately from its parent AP, revealed a tertiary structure similar to the open structure of saposin C and forms a homodimer at pH 7.4. The first helix on the N-terminal end of the open structure of potato PSI also shows similarity in its tertiary structure to the hemagglutinin fusion peptide, exhibiting a similar boomerang motif. As well, this helix shares the overall helix-kink-helix shape with hemagglutinin induced by the presence of a tryptophan; this revelation is important as it suggests a reason for the N-terminal side helix interaction with phospholipid bilayers.
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Chhitar Mal Gupta (born 1944) is an Indian molecular biologist and academic, known for researches on transbilayer phospholipid asymmetry in biological membranes., drug targeting in parasitic diseases and characterization of structure and function of Leishmania actin and actin binding proteins. He is former director of the Central Drug Research Institute, Lucknow and the Institute of Microbial Technology, Chandigarh. A Distinguished Biotechnology Fellow and Distinguished Biotechnology Research Professor of the Department of Biotechnology, Government of India, he is an elected fellow of The World Academy of Sciences, Indian Academy of Sciences, Indian National Science Academy, National Academy of Sciences, India and the National Academy of Medical Sciences.
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ITP3K plays a role in regulating or cooperating with intracellular calcium signals that occur following the liberation of inositol trisphosphate. In this pathway, either a G-protein coupled receptor (GPCR) or receptor tyrosine kinase (RTK) is activated by an extracellular ligand-binding event. Initiation of the pathway leads to an activated G-alpha subunit of a heterotrimeric G protein (in the case of GPCR-mediated signal transduction) or autophoshorylation of RTK cytoplasmic domains (in the case of RTK-mediated signal transduction). These intracellular events eventually lead to activation of phospholipase C (PLC), which cleaves the phospholipid PIP2 into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).
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During this transition, proteolytic processing begins to cleave precursor proteins. Once multivescular body reaches the membrane of lamellar body, both membranes fuse together so that processed proteins can be transported into lamellar body, where last steps of maturation for both SP-B and SP-C occur. When lamellar body is ready to be secreted, exocytosis is initiated through influx of Ca2+, and lamellar membrane fuses with plasma membrane to release surfactant phospholipid contents into the surface of the cell. SP-B and SP-C are responsible to carry out adsorption of the lipid monolayer at the liquid-air interphase to prevent post expiration atelectasis.
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The basic premise is that as individual organisms (especially bacteria and fungi) die, phospholipids are rapidly degraded and the remaining phospholipid content of the sample is assumed to be from living organisms. As the phospholipids of different groups of bacteria and fungi contain a variety of somewhat unusual fatty acids, they can serve as useful biomarkers for such groups. PLFA profiles and composition can be determined by purifying the phospholipids and then cleaving the fatty acids for further analysis. Knowledge of the composition and metabolic activity of the microbiota in soils, water and waste materials is useful in optimizing crop production, in bioremediation and in understanding microbial ecosystems.
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Although sterol transfer is proposed to occur at regions where organelle membranes are closely apposed, disruption of endoplasmic reticulum-plasma membrane contact sites do not have major effects on sterol transfer, though phospholipid homeostasis is perturbed. Various ORPs confine at membrane contacts sites (MCS), where endoplasmic reticulum (ER) is apposed with other organelle limiting membranes. Yeast ORPs also participate in vesicular trafficking, in which they affect Sec14-dependent Golgi vesicle biogenesis and, later in post-Golgi exocytosis, they affect exocyst complex-dependent vesicle tethering to the plasma membrane. In mammalian cells, some ORPs function as sterol sensors that regulate the assembly of protein complexes in response to changes in cholesterol levels.
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Vitamin B12 deficiency causes particular changes to the metabolism of two clinically relevant substances in humans: # Homocysteine (homocysteine to methionine, catalysed by methionine synthase) leading to hyperhomocysteinemia # Methylmalonic acid (methylmalonyl- CoA to succinyl-CoA, of which methylmalonyl-CoA is made from methylmalonic acid in a preceding reaction) Methionine is activated to S-adenosyl methionine, which aids in purine and thymidine synthesis, myelin production, protein/neurotransmitters/fatty acid/phospholipid production and DNA methylation. 5-Methyl tetrahydrofolate provides a methyl group, which is released to the reaction with homocysteine, resulting in methionine. This reaction requires cobalamin as a cofactor. The creation of 5-methyl tetrahydrofolate is an irreversible reaction.
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PIP2 cleavage to IP3 and DAG initiates intracellular calcium release and PKC activation. Note: PLC is not an intermediate like the image may confuse, it actually catalyzes the IP3/DAG separation In biochemical signaling, diacylglycerol functions as a second messenger signaling lipid, and is a product of the hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by the enzyme phospholipase C (PLC) (a membrane-bound enzyme) that, through the same reaction, produces inositol trisphosphate (IP3). Although inositol trisphosphate diffuses into the cytosol, diacylglycerol remains within the plasma membrane, due to its hydrophobic properties. IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, whereas DAG is a physiological activator of protein kinase C (PKC).
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For this purpose, a so-called Venturi-tube serves, as well as the above- mentioned surgical hand pieces, being modified to smoke the aerosols through them. Analysis of the flue gas in the mass spectrometer is realized instantaneously, within a few tenths of a second, resulting in a tissue- specific phospholipid mass spectra being obtained, allowing a response by the surgeon in less than two seconds. The analysis of the collected spectra is made of special-evaluation software, which was developed for this purpose. The software continuously compares the incoming data during surgery, validates mass spectra stored in a database, assigns the appropriate class, and the result is displayed visually to the surgeon.
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At the same time in Germany, Hansjörg Eibl, at the Max Planck Institute for Biophysical Chemistry, and Clemens Unger, at the University of Göttingen, demonstrated that the antineoplastic activity of the phospholipid analogue miltefosine (at the time known as hexadecylphosphocholine) was indeed tumour- specific. It was highly effective against methylnitrosourea-induced mammary carcinoma, but less so on transplantable mammary carcinomas and autochthonous benzo(a)pyrene-induced sarcomas, and relatively inactive on Walker 256 carcinosarcoma and autochthonous acetoxymethylmethylnitrosamine-induced colonic tumors of rats. It was subsequently found that miltefosine was structurally unique among lipids having anticancer property in that it lacks the glycerol group, is highly selective on cell types and acts through different mechanism.
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A glucagon receptor, upon binding with the signaling molecule glucagon, initiates a signal transduction pathway that begins with the activation of adenylate cyclase, which in turn produces cyclic AMP (cAMP). Protein kinase A, whose activation is dependent on the increased levels of cAMP, is responsible for the ensuing cellular response in the form of protein kinase 1 and 2. The ligand-bound glucagon receptor can also initiate a concurrent signaling pathway that is independent of cAMP by activating phospholipase C. Phospholipase C produces DAG and IP3 from PIP2, a phospholipid phospholipase C cleaves off of the plasma membrane. Ca2+ stores inside the cell release Ca2+ when its calcium channels are bound by IP3.
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MFGM bioactive protein components, including the glycoproteins lactadherin, MUC-1, and butyrophilin, have been shown in preclinical studies to affect immune response. These components influence the immune system by several mechanisms, including interference with microbe adhesion to intestinal epithelia, bacteriocidal action, support of beneficial microbiota, and modulation of other parts of the immune system. MFGM phospholipid components such as phosphatidylcholine are a key constituent of the intestinal mucus barrier, and therefore may contribute to intestinal defense against invasive pathogens. Sphingolipids, including sphingomyelin, are present in the apical membrane of the gut epithelia, and are also important for maintaining membrane structure, modulating growth factor receptors, and serving competitive binding inhibitors for microorganisms, microbial toxins, and viruses.
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The triterpenes 3α-carboxyacetoxyquercinic acid, 3α-carboxyacetoxy-24-methylene-23-oxolanost-8-en-26-oic acid, and 5α,8α-epidioxyergosta-6,22-dien-3β-ol (ergosterol peroxide) have been isolated from D. confragosa. Lectins from D. confragosa, tested against rabbit and human erythrocytes, were determined to have anti-H serological specificity. Analysis of the lipid and fatty acid composition revealed that D. confragosa contains 20.1% total lipids (mg/g dry weight), 32.9% neutral lipids, 53.8% phospholipid, and 13.3% glycolipids. An analysis of hydroxy fatty acid content showed that D. confragosa contains, as a percentage of total fatty acids, 0.02% 7-hydroxy-8,14-dimethyl-9-hexadecenoic acid and 0.01% 7-hydroxy-8,16-dimethyl-9-octadecenoic acid.
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16- and 18-carbon omega-7 unsaturated fatty acids are known to be converted into 18- or 20-carbon highly unsaturated fatty acids in the body by nonselective desaturating enzymes. The same enzymes also act on omega-3, omega-6, and omega-9 fatty acids. As a result, while proportions of individual highly unsaturated fatty acids may vary greatly in different tissue types due to factors such as diet, the overall concentration of highly unsaturated fatty acids is kept stable in a living organism. These individual concentrations are highly influential in determining what fatty acids will be used by a given tissue type in phospholipid synthesis such as that required for the maintenance of the cellular membrane.
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In enzymology, a phosphatidyl-N-methylethanolamine N-methyltransferase () is an enzyme that catalyzes the chemical reaction :S-adenosyl-L-methionine + phosphatidyl-N-methylethanolamine \rightleftharpoons S-adenosyl-L-homocysteine + phosphatidyl-N-dimethylethanolamine Thus, the two substrates of this enzyme are S-adenosyl methionine and phosphatidyl-N-methylethanolamine, whereas its two products are S-adenosylhomocysteine and phosphatidyl-N- dimethylethanolamine. This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases. The systematic name of this enzyme class is S-adenosyl-L-methionine:phosphatidyl- N-methylethanolamine N-methyltransferase. Other names in common use include phosphatidylmonomethylethanolamine methyltransferase, methyltransferase II, phospholipid methyltransferase, PLMT, phosphatidyl-N-methylethanolamine methyltransferase, phosphatidyl-N-monomethylethanolamine methyltransferase, phosphatidylethanolamine methyltransferase I, and phosphatidylmonomethylethanolamine methyltransferase.
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The fatty acid synthetic pathway is the principal route for the production of membrane phospholipid acyl chains in bacterial and plants. The reaction sequence is carried out by a series of individual soluble proteins that are each encoded by a discrete gene, and the pathway intermediates are shuttled between the enzymes. Malony-CoA:ACP Transacylase (FabD) is one such individual soluble protein and catalyzes the following reaction: :malonyl-CoA + acyl carrier protein CoA + malonyl-[acyl-carrier-protein] The transfer of malonate to acyl-carrier-protein (ACP) converts the acyl groups into thioester forms which are characteristic of acyl intermediates in fatty acid synthesis and which are strictly required for the condensation reactions catalyzed by β-ketoacyl-ACP synthetase.
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The syndrome can be divided into primary (no underlying disease state) and secondary (in association with an underlying disease state) forms. Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH, which in turn inhibits Protein C, a glycoprotein with regulatory function upon the common pathway of coagulation (by degrading activated factor V). Lupus anticoagulant (LAC) antibodies bind to prothrombin, thus increasing its cleavage to thrombin, its active form. In APS there are also antibodies binding to Protein S, which is a co-factor of protein C. Thus, anti-protein S antibodies decrease protein C efficiency. Annexin A5 forms a shield around negatively charged phospholipid molecules, thus reducing their availability for coagulation.
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Note ether at first position, and acetyl group at second position. In an organic chemistry general sense, an ether lipid implies an ether bridge between an alkyl group (a lipid) and an unspecified alkyl or aryl group, not necessarily glycerol. If glycerol is involved, the compound is called a glyceryl ether, which may take the form of an alkylglycerol, an alkyl acyl glycerol, or in combination with a phosphatide group, a phospholipid. In a biochemical sense, an ether lipid usually implies glycerophospholipids of various type, also called phospholipids, in which the sn-1 position of the glycerol backbone has a lipid attached by an ether bond and a lipid attached to the sn-2 position via an acyl group.
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Functional protein microarrays (also known as target protein arrays) are constructed by immobilising large numbers of purified proteins and are used to identify protein–protein, protein–DNA, protein–RNA, protein–phospholipid, and protein–small-molecule interactions, to assay enzymatic activity and to detect antibodies and demonstrate their specificity. They differ from analytical arrays in that functional protein arrays are composed of arrays containing full-length functional proteins or protein domains. These protein chips are used to study the biochemical activities of the entire proteome in a single experiment. The key element in any functional protein microarray-based assay is the arrayed proteins must retain their native structure, such that meaningful functional interactions can take place on the array surface.
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Moving outwards away from the hydrophobic core region and into the interfacial hydrophilic region, the effective concentration of water rapidly changes across this boundary layer, from nearly zero to a concentration of around 2 M. The phosphate groups within phospholipid bilayers are fully hydrated or saturated with water and are situated around 5 Å outside the boundary of the hydrophobic core region (see Figures ). Some water-soluble proteins associate with lipid bilayers irreversibly and can form transmembrane alpha-helical or beta-barrel channels. Such transformations occur in pore forming toxins such as colicin A, alpha-hemolysin, and others. They may also occur in BcL-2 like protein , in some amphiphilic antimicrobial peptides , and in certain annexins .
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It retains its antimicrobial activity when attached back into the parent AP. Atomic force microscopy experimentation on potato PSI expressed separately from its parent AP has revealed that anionic phospholipid membranes are rearranged by PSI in a similar fashion to that observed with saposin C. As well, PSI from potato has also been shown to exhibit Michaelis-Menten-like kinetics, elucidated from large unilamellar vesicle (LUV) disruption assays in a dose-dependent manner, a feature unique among SAPLIPs. The Michaelis-Menten-like kinetics coupled with the PSIs independent function from its parent AP has thus led to the revelation that the PSI is the first known example of an “enzyme within an enzyme”.
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These tissues are known to metabolize arachidonic acid to EETs; it has been shown or is presumed that they also metabolize DHA to EPD's. The EDPs are commonly made by the stimulation of specific cell types by the same mechanisms which produce EETs (see Epoxyeicosatrienoic acid). That is, cell stimulation causes DHA to be released from the sn-2 position of their membrane-bound cellular phospholipid pools through the action of a Phospholipase A2-type enzyme and the subsequent attack of the released DHA by CYP450 epoxidases. It is notable that the consumption of omega-3 fatty acid-rich diets dramatically raises the serum and tissue levels of EDPs and EEQs in animals as well as humans.
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They showed that silicone breast implants did not cause connective tissue diseases or gammopathies; that oral contraceptives did not prevent rheumatoid arthritis; and that women risked developing lupus from oral contraceptives and post-menopausal hormone replacement therapy. They provided the first convincing evidence that the anti-phospholipid antibody was a risk factor for thromboembolic disease in healthy men. The group sorted out the effects of lower socioeconomic status and the characteristics associated with it that could be modified in populations with health disparities. They discovered that self-confidence in self-management and self-monitoring was linked to poorer health status, and then showed an intervention to improve self-efficacy could improve the quality of life in patients with lupus.
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In the cell, Sec14p plays an active and regulatory role in the intracellular transport of proteins. A good example of this function is the ability of Sec14p to both transport the phospholipids PtdIns and PtdCho between membranes as well as the inhibition of phospholipase D1 and phospholipase B1, which convert PtdCho to phosphatidic acid and choline or PtdCho to glycerophosphocholine, respectively. Sec14p and its homologs, some of which exhibit activation of phospholipase D1 and B1, aid in phospholipid metabolism regulation in vivo. Additionally, Sec14p is essential in the budding of vesicles from the Golgi body, as it is thought to serve a function related to preserving diacylglycerol concentration in the Golgi body, a compound essential to secretory vesicle biosynthesis.
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Mutations in the SLC25A46 gene, inherited in an autosomal recessive manner, cause type 6B hereditary motor and sensory neuropathy. Symptoms include early- onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity. Overexpression of this protein causes mitochondrial fragmentation while knockdown of this protein causes mitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission. Loss of this gene also has many other effects: premature cellular senescence, impaired cellular respiration, destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened cristae, altered ER morphology, impaired cell migration, and changes in mitochondrial phospholipid composition.
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The exact biochemical process by which trans fats produce specific health problems are a topic of continuing research. Intake of dietary trans fat perturbs the body's ability to metabolize essential fatty acids (EFAs, including Omega-3) leading to changes in the phospholipid fatty acid composition of the arterial walls, thereby raising risk of coronary artery disease. Trans double bonds are claimed to induce a linear conformation to the molecule, favoring its rigid packing as in plaque formation. The geometry of the cis double bond, in contrast, is claimed to create a bend in the molecule, thereby precluding rigid formations.. While the mechanisms through which trans fatty acids contribute to coronary artery disease are fairly well understood, the mechanism for their effects on diabetes is still under investigation.
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Uteroglobin, also known as secretoglobin family 1A member 1 (SCGB1A1), is a protein that in humans is encoded by the SCGB1A1 gene. SCGB1A1 is the founding member of the secretoglobin family of small, secreted, disulfide-bridged dimeric proteins found only in mammals. This antiparallel disulfide linked homodimeric protein is multifunctional and found in various tissues in various names such as: uteroglobin (UG, UGB), uteroglobin-like antigen (UGL), blastokinin, club-cell secretory protein (CCSP), Clara-cell 16 kD protein (17 in rat/mice), club-cell-specific 10 kD protein (CC10), human protein 1, urine protein 1 (UP-1), polychlorinated biphenyl-binding protein (PCB-BP), human club cell phospholipid-binding protein (hCCPBP), secretoglobin 1A member 1 (SCGB1A1). This protein is specifically expressed in club cells in the lungs.
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Cross-sectional view of the structures that can be formed by phospholipids in an aqueous solution A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates cell from the external environment or creates intracellular compartments. Biological membranes, in the form of eukaryotic cell membranes, consist of a phospholipid bilayer with embedded, integral and peripheral proteins used in communication and transportation of chemicals and ions. The bulk of lipid in a cell membrane provides a fluid matrix for proteins to rotate and laterally diffuse for physiological functioning. Proteins are adapted to high membrane fluidity environment of lipid bilayer with the presence of an annular lipid shell, consisting of lipid molecules bound tightly to surface of integral membrane proteins.
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Generally, small hydrophobic molecules can readily cross phospholipid bilayers by simple diffusion. Particles that are required for cellular function but are unable to diffuse freely across a membrane enter through a membrane transport protein or are taken in by means of endocytosis, where the membrane allows for a vacuole to join onto it and push its contents into the cell. Many types of specialized plasma membranes can separate cell from external environment: apical, basolateral, presynaptic and postsynaptic ones, membranes of flagella, cilia, microvillus, filopodia and lamellipodia, the sarcolemma of muscle cells, as well as specialized myelin and dendritic spine membranes of neurons. Plasma membranes can also form different types of "supramembrane" structures such as caveolae, postsynaptic density, podosome, invadopodium, desmosome, hemidesmosome, focal adhesion, and cell junctions.
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Autophagin-1 (Atg4/Apg4) is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8/Apg8/Aut7, a reaction essential for its lipidation during autophagy.Development by self-digestion: molecular mechanisms and biological functions of autophagy by Levine B, Klionsky DJ. in Dev Cell. 2004 Apr;6(4):463-77. Review. Human Atg4 homologues cleave the carboxyl termini of the three human Atg8 homologues, microtubule-associated protein light chain 3 (LC3), GABARAP, and GATE-16.HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates byTanida I, Sou YS, Ezaki J, Minematsu- Ikeguchi N, Ueno T, Kominami E. in J Biol Chem.
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In seabirds, primaquine has been used in a study to show effective treatment on infected hosts. Treatment for babesiosis consisted of primaquine (1 mg/kg PO q24h for 10 days; primaquine phosphate 1.76%m/v in stabilized solution, Primaquin Solution, MedPet Ltd, Benrose, South Africa). After, treatment was followed by a phospholipid supplement (1 capsule/bird PO q24h for 12 days; deoiled, enriched phospholipids from soybeans, 300 mg/capsule, Essentiale Extreme, Sanofi Aventis Ltd, Midrand, South Africa); as an attempt to mitigate potential hepatotoxic effects of primaquine. To prevent transmission of Babesia and other tickborne pathogens, all birds with visible ectoparasites are treated with pesticide powder (carbaryl 50 g/kg) upon admission, and the facilities are thoroughly cleaned on a daily basis.
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Although the exact mechanism of formation of lipid droplets is still unknown, it is proposed that they bud off the membrane of the endoplasmic reticulum as TAGs are collected between the two layers of its phospholipid membrane. Lipid droplet growth can consequently happen through direct diffusion of fatty acids, endocytosis of sterols or by fusion of smaller lipid droplets through the aid of SNARE proteins. Lipid droplets have also been observed to be created by the fission of existing lipid droplets, though this is thought to be less common than de novo formation. Lipid droplets visualized with label-free live cell imaging The formation of lipid droplets from the endoplasmic reticulum begins with the synthesis of the neutral lipids to be transported.
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In response to a mechanical stimulus, cellular sensors of force are proposed to be extracellular matrix molecules, cytoskeleton, transmembrane proteins, proteins at the membrane-phospholipid interface, elements of the nuclear matrix, chromatin, and the lipid bilayer. Response can be twofold: the extracellular matrix, for example, is a conductor of mechanical forces but its structure and composition is also influenced by the cellular responses to those same applied or endogenously generated forces. Mechanosensitive ion channels are found in many cell types and it has been shown that the permeability of these channels to cations is affected by stretch receptors and mechanical stimuli. This permeability of ion channels is the basis for the conversion of the mechanical stimulus into an electrical signal..
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Hong grew up in China and completed her bachelor's degree in Chemistry from Mount Holyoke College (summa cum laude) in 1992. She received her Ph.D. degree from the University of California, Berkeley in the laboratory of Alexander Pines in 1996, where she investigated phospholipid structure and dynamics using variable-angle-spinning NMR. After a one-year postdoctoral stint in the laboratory of Robert G. Griffin at the Massachusetts Institute of Technology, she went to University of Massachusetts Amherst and developed biosynthetic isotopic labeling approaches to advance protein structure determination by ssNMR. She started an assistant professorship at Iowa State University in 1999, became an associate professor in 2002 and full professor in 2004, and held the first John D. Corbett Professorship from 2007 to 2010.
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Some types of phospholipid can be split to produce products that function as second messengers in signal transduction. Examples include phosphatidylinositol (4,5)-bisphosphate (PIP2), that can be split by the enzyme Phospholipase C into inositol triphosphate (IP3) and diacylglycerol (DAG), which both carry out the functions of the Gq type of G protein in response to various stimuli and intervene in various processes from long term depression in neurons to leukocyte signal pathways started by chemokine receptors. Phospholipids also intervene in prostaglandin signal pathways as the raw material used by lipase enzymes to produce the prostaglandin precursors. In plants they serve as the raw material to produce Jasmonic acid, a plant hormone similar in structure to prostaglandins that mediates defensive responses against pathogens.
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31P-NMR spectroscopy is widely used for studies of phospholipid bilayers and biological membranes in native conditions. The analysis of 31P-NMR spectra of lipids could provide a wide range of information about lipid bilayer packing, phase transitions (gel phase, physiological liquid crystal phase, ripple phases, non bilayer phases), lipid head group orientation/dynamics, and elastic properties of pure lipid bilayer and as a result of binding of proteins and other biomolecules. In addition, a specific N-H...(O)-P experiment (INEPT transfer using three-bond scalar coupling 3JN-P~5 Hz) could provide a direct information about formation of hydrogen bonds between amine protons of protein to phosphate of lipid headgroups, which is useful in studies of protein/membrane interactions.
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While warfarin is one of several drugs popularly referred to as a "blood thinner", this is a misnomer since it does not affect the viscosity of blood. Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z. Other proteins not involved in blood clotting, such as osteocalcin, or matrix Gla protein, may also be affected. The precursors of these factors require gamma carboxylation of their glutamic acid residues to allow the coagulation factors to bind to phospholipid surfaces inside blood vessels, on the vascular endothelium. The enzyme that carries out the carboxylation of glutamic acid is gamma-glutamyl carboxylase.
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Additionally, sustained ERK activity seems to be important for phosphorylation and nuclear localization of CDK2, further supporting progression through the restriction point. PI3K Pathway Signaling p85, another SH2-domain-containing protein, binds activated RTKs and recruits PI3K (phosphoinositide-3-kinase), phosphorylating the phospholipid PIP2 to PIP3, leading to recruitment of Akt (via its PH-domain). In addition to other pro-growth and pro-survival functions, Akt inhibits glycogen synthase kinase-3β (GSK3β), thereby preventing GSK3β -mediated phosphorylation and subsequent degradation of cyclin D1 (see figure). Akt further regulates G1/S components by mTOR-mediated promotion of cyclin D1 translation, phosphorylation of the Cdk inhibitors p27kip1 (preventing its nuclear import) and p21Cip1 (decreasing stability), and inactivating phosphorylation of the transcription factor FOXO4 (which regulates p27 expression).
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The encoded protein may also play a role in phospholipid remodelling, arachidonic acid release, nitric oxide-induced or vasopressin-induced arachidonic acid release and in leukotriene and prostaglandin synthesis, Fas receptor-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. It addition, it has a role in cardiolipin (CL) deacylation, and is required for both speed and directionality of monocyte MCP1/CCL2-induced chemotaxis through regulation of F-actin polymerization at the pseudopods. Isoform ankyrin-iPLA2-1 and isoform ankyrin-iPLA2-2, which lack the catalytic domain, are probably involved in the negative regulation of PLA2G6 activity. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date.
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The cellular membrane of N. sinuspersici is also unique among other sinuspersici, most notable lacking mycolic acids. Strains of N. sinuspersici can grow in a wide range of conditions, but have been found to grow best at 28 C, a pH of 7, and a salt concentration of 2.5%. Despite showing high similarity genetic similarity to Nocardiopsis quinghaiensis, Nocardiopsis aegyptia, and Nocardiopsis halotolerans, N. sinuspersici shows a distinguishable growth rate among other species when grown at a pH of 12, a salt concentration of 15%, and a temperature of 10 C. N. sinuspersici is also distinguishable from the other members of Nocardiopsis among major chemical compounds, including the producion of different sugars, phospholipid patterns, menaquinones, and fatty acids. The bacterium also produces a serine protease capable of rapidly breaking down milk protien.
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Cardiolipin is a mitochondrion-specific phospholipid found in both the mitochondrial inner and outer membranes Many studies speculate that cardiolipin is a likely player in mitochondrial apoptosis. In a study done by R Lee et al., it was found that during apoptosis, cardiolipin in the outer membrane of the mitochondria increased from 10% to 30% saturation. Finding that cardiolipin concentration in the outer mitochondrial membrane increased during apoptosis (as well as knowing the function that PLS3 plays in mitochondrial apoptotic effects) clued Lee in to the fact that PLS3 may have effects on this cardiolipin membrane redistribution. Lee’s study looked into the consequences of cardiolipin redistribution in the mitochondria and found that cardiolipin plays a critical role in proteins that are involved with oxidative respiration (such as ATP synthase), which in turn affects ATP production.
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Cholesterol, given that it composes about 30% of all animal cell membranes, is required to build and maintain membranes and modulates membrane fluidity over the range of physiological temperatures. The hydroxyl group of each cholesterol molecule interacts with water molecules surrounding the membrane, as do the polar heads of the membrane phospholipids and sphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which both alters membrane fluidity and maintains membrane integrity so that animal cells do not need to build cell walls (like plants and most bacteria). The membrane remains stable and durable without being rigid, allowing animal cells to change shape and animals to move.
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Since free-radical-induced and singlet-oxygen-induced oxidations of linoleic acid produce a similar set of 13-HODE metabolites (see 13-Hydroxyoctadecadienoic acid), since both free radicals and singlet oxygen attack not only free linoleic acid but also linoleic acid bound to phospholipids, glycerides, cholesterol, and other lipids, and since free- radical and singlet-oxygen reactions may occur together, oxygen-stressed tissues often contain an array of free and lipid-bound 9-HODE and 13-HODE products. For example, laboratory studies find that 9-HODE and 9-EE-HODE (along with their 13-HODE counterparts) are found in the phospholipid and cholesterol components of low-density lipoproteins that have been oxidized by human monocytes; the reaction appears due to the in situ free-radical- and/or superoxide-induced oxidation of the lipoproteins.
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At approximately 8 mol% of cholesterol the start of the liquid-disordered phase begins. This same relationship is observed in the DSPC, cholesterol, and exchanging lipids 2 and 3 but the start of the liquid- disorder phase occurs at approximately 5.2 mole% with and without the presence of ethanol. Also, there is a higher equilibrium constant value in which the studies relate it to the stronger acyl chain interactions due to this region having longer carbon chains which results in a higher melting point as well. This study not only proves that in the presence of ethanol a reorganization or induced phase change takes place between the cholesterol-phospholipid interaction but that by using higher concentrations of sterol compounds like cholesterol it can hinder the effects of ethanol.
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A polymerase (L) gene-specific siRNAs delivery system was imposed upon four genes associated with the viral genomic RNA in the ribonucleoprotein complex found within EBOV particles (three of which match the application above): NP, VP30, VP35, and the L protein. The SNALPs ranged from 71 – 84 nm in size and were composed of synthetic cholesterol, phospholipid DSPC, PEG lipid PEGC-DMA, and cationic lipid DLinDMA at the molar ratio of 48:20:2:30. The results confirm complete protection against viremia and death in guinea pigs when administered a SNALP-siRNA delivery system after diagnosis of the Ebola virus, thus proving this technology to be an effective treatment. Future studies will focus mainly upon evaluating the effects of siRNA ‘cocktails’ on EBOV genes to increase antiviral effects.
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Additional studies have been designed to explore the function of UAS in more detail largely in part because a large number of phospholipid biosynthetic enzyme activities in the model organism Saccharomyces cerevisiae show this common pattern of expression. One study explored the interaction between Ino4p and Ino2p in more depth, examining the dimerization that takes place between the two prior to binding to the promoter of the INO1 gene and activating transcription. By isolating 31 recessive suppressors of the ino4-8 mutant of yeast and determining that 29 were of the same locus, the researchers identified the locus as REG1 . One allele of REG1, the suppressor mutant sia1-1, was capable of suppressing the inositol auxotrophy, revealing a possible pathway for the repression of inositol- sensitive upstream activating sequence-containing genes of yeast.
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Nucleus 2 Nuclear pore 3 Rough endoplasmic reticulum (RER) 4 Smooth endoplasmic reticulum (SER) 5 Ribosome on the rough ER 6 Proteins that are transported 7 Transport vesicle 8 Golgi apparatus 9 Cis face of the Golgi apparatus 10 Trans face of the Golgi apparatus 11 Cisternae of the Golgi apparatus 3D rendering of endoplasmic reticulum The general structure of the endoplasmic reticulum is a network of membranes called cisternae. These sac-like structures are held together by the cytoskeleton. The phospholipid membrane encloses the cisternal space (or lumen), which is continuous with the perinuclear space but separate from the cytosol. The functions of the endoplasmic reticulum can be summarized as the synthesis and export of proteins and membrane lipids, but varies between ER and cell type and cell function.
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Passive diffusion on a cell membrane. However; in a case of auxins, only the non-dissociated portion of auxin molecules is able to cross the membrane As weak acids, the protonation state of auxins is dictated by the pH of the environment; a strongly acidic environment inhibits the forward reaction (dissociation), whereas an alkaline environment strongly favors it (see Henderson-Hasselbalch equation): The export of auxins from cells is termed auxin efflux and the entry of auxin in to cells is called auxin influx. The first step in polar transport is auxin influx. Auxin enters plant cells by two methods, first by passive diffusion as non-ionized IAA molecule or the protonated form as IAAH across the phospholipid bilayer, or second by active co-transport in the anionic form IAA−.
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The underlying function of proteins belonging to the SAPLIP group is to interact with membrane bilayers, either by perturbation (without permeabilization), permeabilization of the membrane or binding to the membrane. Notable members of the SAPLIP family include granulysin (antimicrobial), pulmonary surfactant-associated protein B (pulmonary surfactant regulation) and the saposins (sphingolipid degradation) of which SAPLIPs are named after. Specific to the PSI, it has been shown that PSI is involved in mediating interactions of the PSI, both alone and in combination with the PSI’s parent enzyme, with phospholipid membranes at acidic pH (~pH 4.5). Specifically, the PSI is involved in vacuolar targeting and membrane perturbation; this enables both the storage and movement of the AP into protein storage compartments within vacuoles contained in both leaves and roots of barley and cardoon.
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13-HODE, 13-oxoODE, and 13-EE-HODE (along with their 9-HODE counterparts) directly activate peroxisome proliferator- activated receptor gamma (PPARγ). This activation appears responsible for the ability of 13-HODE (and 9-HODE) to induce the transcription of PPARγ-inducible genes in human monocytes as well as to stimulate the maturation of these cells to macrophages. 13(S)-HODE (and 9(S)-HODE) also stimulate the activation of peroxisome proliferator-activated receptor beta (PPARβ) in a model cell system; 13-HODE (and 9-HODE) are also proposed to contribute to the ability of oxidized low-density lipoprotein (LDL) to activate PPARβl: LDL containing phospholipid-bound 13-HODE (and 9-HODE) is taken up by the cell and then acted on by phospholipases to release the HODEs which in turn directly activate PPARβl.
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Lahita is a clinical professor at New Jersey Medical School, an adjunct professor at the Icahn School of Medicine at Mount Sinai, and a full professor of medicine at New York Medical College. He is a fellow of the American College of Physicians, a master of the American College of Rheumatology, a fellow of the Royal College of Physicians, a Fellow of the Royal Society of Medicine, and a Fellow of the New York Academy of Sciences. His research interests are the molecular aspects of antigen expression in response to sex hormones in the autoimmune diseases, reasons for female predisposition of autoimmune disease, and the etiopathogenesis of the phospholipid syndrome. Lahita is the editor of the standard textbook Systemic Lupus Erythematosus (5th edition), and the Senior Editor of the Textbook of Autoimmune Diseases.
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Though lacking a cell wall, F. acidiphilum cell membranes contain caldarchaetidylglycerol tetraether lipids, which effectively block almost all proton access, Thermoplasma acidophilum also uses these bulky isoprenoid cores in its phospholipid bilayer. It is possible that the family Ferroplasmaceae may in fact be more important in AMD than the current paradigm, Acidithiobacillaceae. From a practical viewpoint this changes little, as despite the myriad physiological differences between archaea and bacteria, treatments would remain the same; if pH is kept high, and water and oxygen are prohibited from the pyrite, the reaction will be negligible. The isolation from solfataric soils of two Picrophilus species of archaea P.oshimae and P.torridus are of note for their record low of survival at pH 0, indicating that further AMD microorganisms may remain to be found which operate at an even lower pH.
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Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: factors VII, IX, X and protein C. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces. The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI, but this reaction does not require the presence of protein Z. In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis.
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Oxidation of fatty acids Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants. In addition, fatty acids are important components of the phospholipids that form the phospholipid bilayers out of which all the membranes of the cell are constructed (the plasma membrane and other membranes that enclose all the organelles within the cells, such as the nucleus, the mitochondria, endoplasmic reticulum, and the Golgi apparatus). Fatty acids can also be cleaved, or partially cleaved, from their chemical attachments in the cell membrane to form second messengers within the cell, and local hormones in the immediate vicinity of the cell. The prostaglandins made from arachidonic acid stored in the cell membrane, are probably the most well known group of these local hormones.
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Myristic acid is commonly added to the N-terminus glycine in receptor-associated kinases to confer the membrane localization of the enzyme. The myristic acid has a sufficiently high hydrophobicity to become incorporated into the fatty acyl core of the phospholipid bilayer of the plasma membrane of the eukaryotic cell. In this way, myristic acid acts as a lipid anchor in biomembranes. Various "human epidemiological studies have shown that myristic acid and lauric acid were the saturated fatty acids most strongly related to the average serum cholesterol concentrations in humans", meaning they were positively correlated with higher cholesterol levels as well as raising triglycerides in plasma by some 20% increasing the risk for cardiovascular disease, although some research points to myristic acid's positive effects on HDL cholesterol and hence improving HDL (good cholesterol) to total cholesterol ratio.
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Blue boxes are enzymes important in transitioning to a cancer metabolic phenotype; orange boxes are enzymes that are mutated in cancer cells. Green ovals are oncogenes that are up-regulated in cancer; red ovals are tumor suppressors that are down-regulated in cancer. The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. The characteristic attributes of the tumor metabolome are high glycolytic enzyme activities, the expression of the pyruvate kinase isoenzyme type M2, increased channeling of glucose carbons into synthetic processes, such as nucleic acid, amino acid and phospholipid synthesis, a high rate of pyrimidine and purine de novo synthesis, a low ratio of Adenosine triphosphate and Guanosine triphosphate to Cytidine triphosphate and Uridine triphosphate, low Adenosine monophosphate levels, high glutaminolytic capacities, release of immunosuppressive substances and dependency on methionine.
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In enzymology, an acyl-[acyl-carrier-protein]-phospholipid O-acyltransferase () is an enzyme that catalyzes the chemical reaction :acyl-[acyl-carrier protein] + O-(2-acyl-sn-glycero-3-phospho)ethanolamine \rightleftharpoons [acyl-carrier protein] + O-(1,2-diacyl-sn-glycero-3-phospho)ethanolamine Thus, the two substrates of this enzyme are acyl-acyl-carrier protein and O-(2-acyl- sn-glycero-3-phospho)ethanolamine, whereas its two products are acyl-carrier protein and O-(1,2-diacyl-sn-glycero-3-phospho)ethanolamine. This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is acyl-[acyl-carrier protein]:O-(2-acyl-sn- glycero-3-phospho)ethanolamine O-acyltransferase. Other names in common use include acyl-[acyl-carrier, protein]:O-(2-acyl-sn- glycero-3-phospho)-ethanolamine, and O-acyltransferase.
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Principle of FRAP A) The bilayer is uniformly labeled with a fluorescent tag B) This label is selectively photobleached by a small (~30 micrometre) fast light pulse C) The intensity within this bleached area is monitored as the bleached dye diffuses out and new dye diffuses in D) Eventually uniform intensity is restored Fluorescence recovery after photobleaching (FRAP) is a method for determining the kinetics of diffusion through tissue or cells. It is capable of quantifying the two dimensional lateral diffusion of a molecularly thin film containing fluorescently labeled probes, or to examine single cells. This technique is very useful in biological studies of cell membrane diffusion and protein binding. In addition, surface deposition of a fluorescing phospholipid bilayer (or monolayer) allows the characterization of hydrophilic (or hydrophobic) surfaces in terms of surface structure and free energy.
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Krill oil is an extract prepared from a species of Antarctic krill, Euphausia superba. Two of the most important components in krill oil are omega-3 fatty acids similar to those in fish oil, and phospholipid-derived fatty acids (PLFA), mainly phosphatidylcholine (alternatively referred to as marine lecithin). Studies have shown toxic residues in Antarctic krill and fish; however, the United States Food and Drug Administration has accepted notices from krill oil manufacturers declaring that krill oil and products derived from it meet the standards for Generally Recognized as Safe (GRAS) status, although the FDA itself has not tested the products. While not an endangered species, Antarctic krill are a mainstay of the diets of many ocean-based species including whales and there is some environmental and scientific concern that their population has decreased dramatically both due to climate change and human harvesting.
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15-lipoxygenase 1 (ALOX15), while best known for converting the 20 carbon polyunsaturated fatty acid, arachidonic acid, into a series of 15-hydroxylated arachidonic acid metabolites (see 15-hydroxyicosatetraenoic acid), actually prefers as its substrate the 18 carbon polyunsaturated fatty acid, linoleic acid, over arachidonic acid, converting it to 13-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE). The enzyme acts in a highly stereospecific manner, forming 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13(S)-HpODE) but comparatively little or no 13(R)-hydroperoxy-9Z,11E-octadecadienoic acid (13(R)-HpODE) -. In cells, 13(S)-HpODE is rapidly reduced by peroxidases to 13(S)-HODE. ALOX15 is fully capable of metabolizing the linoleic acid that is bound to phospholipid or cholesterol to form 13(S)-HpODE-bound phospholipids and cholesterol that are rapidly converted to their corresponding 13(S)-HODE-bound products.
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The mitochondria-associated ER membrane (MAM) is another structural element that is increasingly recognized for its critical role in cellular physiology and homeostasis. Once considered a technical snag in cell fractionation techniques, the alleged ER vesicle contaminants that invariably appeared in the mitochondrial fraction have been re-identified as membranous structures derived from the MAM—the interface between mitochondria and the ER. Physical coupling between these two organelles had previously been observed in electron micrographs and has more recently been probed with fluorescence microscopy. Such studies estimate that at the MAM, which may comprise up to 20% of the mitochondrial outer membrane, the ER and mitochondria are separated by a mere 10–25 nm and held together by protein tethering complexes. Purified MAM from subcellular fractionation has been shown to be enriched in enzymes involved in phospholipid exchange, in addition to channels associated with Ca2+ signaling.
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This is tested for by using a minimum of two coagulation tests that are phospholipid- sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged partial thromboplastin time (PTT) that does not correct in an 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The PTT (plus 80:20 mix), dilute Russell's viper venom time (DRVVT), kaolin clotting time (KCT), dilute thromboplastin time (TDT/DTT), silica clotting time (SCT) and prothrombin time (using a lupus sensitive thromboplastin) are the principal tests used for the detection of lupus anticoagulant. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion, demonstrating persistent positivity, to allow a diagnosis of antiphospholipid syndrome.
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Bavituximab was invented at University of Texas Southwestern Medical Center at Dallas; Peregrine Pharmaceuticals exclusively licensed intellectual property related to bavituximab from the university, including US patent 6,300,308 invented by Alan J. Schroit and US Patents 6,406,693 and 6,312,694 invented in the laboratory Philip E. Thorpe.Peregrine's Annual Report for the fiscal year ended April 30, 2015Peregrine press release: Peregrine Pharmaceuticals Licenses Additional Intellectual Property for Its Anti-Phospholipid Therapy Platform Technology . July 6, 2004 As of January 2016, bavituximab had been in a Phase III clinical trial for non-small cell lung cancer (NSCLC),Phase 3 Study of Bavituximab Plus Docetaxel Versus Docetaxel Alone in Patients With Late-stage Non-squamous Non-small-cell Lung Cancer (SUNRISE) a Phase II/III trial for breast cancer, a Phase II trial for pancreatic cancer, a phase I/II trial for hepatocellular carcinoma, and Phase I clinical trials in malignant melanoma and rectal cancer; its development had been discontinued for influenza and prostate cancer.Staff, Adis Insight.
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9-HODE, 9-oxoODE, and 9-EE-HODE (along with their 13-HODE counterparts) directly activate peroxisome proliferator- activated receptor gamma (PPARγ).Cell. 1998 Apr 17;93(2):229-40Nat Struct Mol Biol. 2008 Sep;15(9):924-31Biol Pharm Bull. 2009 Apr;32(4):735-40 This activation appears responsible for the ability of 13-HODE (and 9-HODE) to induce the transcription of PPARγ-inducible genes in human monocytes as well as to stimulate the maturation of these cells to macrophages. 13(S)-HODE (and 9(S)-HODE) also stimulate the activation of peroxisome proliferator-activated receptor beta (PPARβ) in a model cell system; 13-HODE (and 9-HODE) are also proposed to contribute to the ability of oxidized low-density lipoprotein (LDL) to activate PPARβl: LDL containing phospholipid-bound 13-HODE (and 9-HODE) is taken up by the cell and then acted on by phospholipases to release the HODEs which in turn directly activate PPARβl.
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The experimental method and analytical technique is quite different. In the previous study, it emphasized the NNR technique using a set of host phospholipids, exchanging lipids, ethanol, and cholesterol to create model membranes. An aqueous solution containing 5% ethanol (v/v) was maintained but the concentration of cholesterol was varied to prove how this sterol compound can inhibit the effects of ethanol (inducing a liquid-disorder phase or non-lamellar phases) which is depicted in the different plots of the equilibrium constant (K) versus the mol% of cholesterol for each model membrane. In this study, phospholipid membrane is comparable to the model membrane which consists of POPC, ethanol, water and in some cases the addition of monovalent ions (Na+, K+, and Cl−) that are transported throughout the membrane in the presence of ethanol. The concentration of ethanol varies ranging from 2.5 to 30 mol% in an aqueous solution but there is no addition of any sterol compound.
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Mutations in ferlins can cause human diseases such as muscular dystrophy and deafness. Abnormalities in expression of myoferlin, a human ferlin protein, is also directly associated with higher mortality rate and tumor recurrence in several types of cancer, including pancreatic, colorectal, breast, cervical, stomach, ovarian, cervical, thyroid, endometrial, and oropharyngeal squamous cell carcinoma. In other animals, ferlin mutations can cause infertility. Ferlins are type II transmembrane proteins (N-terminus on the cytoplasmic side of the membrane) and contain five to seven C2 domains linked in tandem and have a single-pass transmembrane domain located at the C-terminus. The C2 domains are denoted in order from amino-terminus to carboxyl-terminus as C2A to C2G. C2 domains are essentially calcium and phospholipid binding domains, evolved for cell membrane interactions. In fact, many proteins involved in signal transduction, membrane trafficking, and membrane fusion employ C2 domains to target the cell membrane. However, ferlins are unique for containing more C2 domains than any other proteins (between five and seven).
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Van Oudenaarden was born 19 March 1970, in Zuidland, a small town in the Dutch province of South Holland. He studied at the Delft University of Technology, where he obtained an MSc degree in Materials Science and Engineering (cum laude) and an MSc degree in Physics, both in 1993, and subsequently a PhD degree in Physics (cum laude) in 1998 in experimental condensed matter physics, under the supervision of professor J.E. Mooij. He received the Andries Miedema Award (best doctoral research in the field of condensed matter physics in the Netherlands) for his thesis on "Quantum vortices and quantum interference effects in circuits of small tunnel junctions". In 1998, he moved to Stanford University, where he was a postdoctoral researcher in the departments of Biochemistry and of Microbiology & Immunology, working on force generation of polymerising actin filaments in the Theriot lab and a postdoctoral researcher in the department of Chemistry, working on Micropatterning of supported phospholipid bi-layers in the Boxer lab.
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In contrast to the closely homologous PKM1, which always occurs in a highly active tetrameric form and which is not allosterically regulated, PKM2 may occur in a tetrameric form but also in a dimeric form. The tetrameric form of PKM2 has a high affinity to its substrate phosphoenolpyruvate (PEP), and is highly active at physiological PEP concentrations. When PKM2 is mainly in the highly active tetrameric form, which is the case in differentiated tissues and most normal proliferating cells, glucose is converted to pyruvate under the production of energy. Meanwhile, the dimeric form of PKM2 is characterized by a low affinity to its substrate PEP and is nearly inactive at physiological PEP concentrations. When PKM2 is mainly in the less active dimeric form, which is the case in tumor cells, all glycolytic intermediates above pyruvate kinase accumulate and are channelled into synthetic processes, which branch off from glycolytic intermediates such as nucleic acid-, phospholipid-, and amino acid synthesis.
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It is possible that the exposure of cholesterol at the membrane surface might be facilitated by other membrane- damaging toxins secreted such as phospholipase C, which cleave the head groups of phospholipids increasing the exposure of cholesterol. Two organisms, Clostridium perfringens that produces perfringolysin O (CDC) and α-toxin during clostridial myonecrosis and Listeria monocytogenes which releases listeriolysin O (CDC) and phospholipases C leading to the virulence of these bacteria. However, although the C. perfringens α-toxin treatment of liposome membranes increase the activity of PFO on those membranes this affect does not appear to aways be the case "in vivo". During C. perfringens gas gangrene (myonecrosis) the main site of action of the C. perfringens α-toxin is the muscle tissue, where the cleavage of the phospholipid head groups does not seem to increase the activity of perfringolysin O on this tissue, as knockouts of PFO do not appear to significantly alter the course of the myonecrosis.
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The manufacture of TAGs from diacylglycerol (by the addition of a fatty acyl chain) is catalyzed by the DGAT proteins, though the extent to which these and other proteins are required depends on cell type. Neither DGAT1 nor DGAT2 is singularly essential for TAG synthesis or droplet formation, though mammalian cells lacking both cannot form lipid droplets and have severely stunted TAG synthesis. DGAT1, which seems to prefer exogenous fatty acid substrates, is not essential for life; DGAT2, which seems to prefer endogenously synthesized fatty acids, is. In non-adipocytes, lipid storage, lipid droplet synthesis and lipid droplet growth can be induced by various stimuli including growth factors, long-chain unsaturated fatty acids (including oleic acid and arachidonic acid), oxidative stress and inflammatory stimuli such bacterial lipopolysaccharides, various microbial pathogens, platelet-activating factor, eicosanoids, and cytokines. An example is the endocannabinoids that are unsaturated fatty acid derivatives, which mainly are considered to be synthesised “on demand” from phospholipid precursors residing in the cell membrane, but may also be synthesised and stored in intracellular lipid droplets and released from those stores under appropriate conditions.
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Mabel and Lowell Hokin conducted research in fundamental biochemistry together from their doctoral research days in Sheffield, to their work at McGill University in the 1950s, up to the mid-1960s at the University of Wisconsin. From the mid-1960s, Mabel worked in her own areas of research with a particular focus on neurochemistry after she received a primary appointment in the Department of Psychiatry along with a joint appointment in the Department of Physiological Chemistry in the University of Wisconsin Medical School. Mabel and Lowell's most significant work came very early in their careers, and was first published in their seminal 1953 paper in the Journal of Biological Chemistry. In it, Mabel and Lowell described experiments in which they stimulated enzyme secretion in slices of pigeon pancreas in the presence of media containing the radioisotope P32. They found that the phospholipid fraction from the stimulated slices, formerly thought to contain fairly inert structural components of cell membranes, contained up to 9 times as much P32 as it did in the non-stimulated control samples.
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Throughout his career, Jean Gruenberg and his colleagues identified several molecular factors directing endosomal biogenesis and dynamics, including various cytoskeleton-associated proteins, the small GTPases Rab5 and Rab7, Annexin A2 (previously named Annexin II), the vacuolar ATPase, COP coat proteins, the N-ethylmaleimide sensitive factor, the small transmembrane proteins of the p24 family, the p38 MAP kinase, phosphatidylinositol-3-phosphate, intra-endosomal cholesterol, the redox sensor thioredoxin-like protein, sorting nexins, the adaptor protein complex AP1, components of ESCRTs and associated proteins and the atypical phospholipid LBPA/BMP (see next section). Using the Vesicular Stomatitis Virus (VSV) as a “hijacker” of the endocytic pathway, Jean Gruenberg and his colleagues demonstrated that intralumenal vesicles present within multivesicular endosomes are able to undergo back-fusion with the limiting membrane of these organelles, thus releasing their content into the cytoplasm, a process regulated by the ESCRT-related proteins TSG101 and ALIX, and since shown to be exploited by various other invaders of the cells such as the Anthrax toxin, and several other viruses.
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In enzymology, a glycosylphosphatidylinositol diacylglycerol-lyase () is an enzyme that catalyzes the chemical reaction :6-(alpha-D- glucosaminyl)-1-phosphatidyl-1D-myo-inositol \rightleftharpoons 6-(alpha-D- glucosaminyl)-1D-myo-inositol 1,2-cyclic phosphate + 1,2-diacyl-sn-glycerol Hence, this enzyme has one substrate, 6-(alpha-D- glucosaminyl)-1-phosphatidyl-1D-myo-inositol, and two products, 6-(alpha-D- glucosaminyl)-1D-myo-inositol 1,2-cyclic phosphate and 1,2-diacyl-sn-glycerol. This enzyme belongs to the family of lyases, specifically the class of phosphorus-oxygen lyases. The systematic name of this enzyme class is 6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol 1,2-diacyl-sn- glycerol-lyase [6-(alpha-D-glucosaminyl)-1D-myo-inositol 1,2-cyclic phosphate- forming]. Other names in common use include (glycosyl)phosphatidylinositol- specific phospholipase C, GPI-PLC, GPI-specific phospholipase C, VSG-lipase, glycosyl inositol phospholipid anchor-hydrolyzing enzyme, glycosylphosphatidylinositol-phospholipase C, glycosylphosphatidylinositol- specific phospholipase C, variant-surface-glycoprotein phospholipase C, 6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol, and diacylglycerol- lyase (1,2-cyclic-phosphate-forming).
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In the most common means for its production, cells make 5-oxo-ETE in a four step pathway that involves their stimulus-induced activation of the following pathway: a) the release of arachidonic acid (i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid) from its storage sites in membrane phospholipids due to the activation of phospholipase A2 enzymes; b) oxygenation of this arachidonic acid by activated arachidonate 5-lipoxygenase (ALOX5) to form 5(S)-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5(S)-HpETE); c) reduction of this 5(S)-HpETE by ubiquitous cellular peroxidases to form 5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5(S)-HETE); and (d) the oxidation of 5(S)-HETE by a microsome-bound nicotinamide adenine dinucleotide phosphate (NADP+)-dependent dehydrogenase enzyme viz., (5-Hydroxyeicosanoid dehydrogenase or 5-HEDH) to form 5-oxo-ETE: a) Phospholipid-bound arachidonic acid → free arachidonic acid b) Free arachidonic acid + O2 → 5(S)-HpETE c) 5(S)-HpETE → 5(S)-HETE d) 5(S)-HETE + NADP+ \rightleftharpoons 5-oxo-ETE + NADPH 5-HEDH has little or no ability to metabolize the R stereoisomer of 5(S)-HETE viz., 5(R)-HETE, to 5-oxo-ETE.
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