"The biggest problem," he says, is that the UCR scientists are claiming that the sterol is being made by the sponges alone.
|
|
"We are interested in identifying the genes involved in unconventional steroid synthesis that makes the sterol precursors of 26-mes," Love said.
|
|
"Patients can feel confident that soy will help lower cholesterol in the same way as other FDA approved plant foods such as nuts, oats and barley, psyllium products and plant sterol margarines," said Dr. David J.A. Jenkins, lead study author and a nutrition researcher at the University of Toronto in Canada.
|
|
Here's the set: 23A: "The Old Gray Mare" = THE OLD GRAY MERYL 31A: Bartlett pear = BARTLETT PERIL 52A: Kodiak bear = KODIAK BARREL 72A: Market share = MARKET SHERYL 143A: Bill of fare = BILL OF FERRELL 104A: Handle with care = HANDLE WITH CAROL 35D: Icy stare = ICY STEROL 48D: Thin air = THIN ERROL 1A: I got this through the 2D and 4D crossings.
|
|
In enzymology, a sterol 3beta-glucosyltransferase () is an enzyme that catalyzes the chemical reaction :UDP-glucose + a sterol \rightleftharpoons UDP + a sterol 3-beta-D-glucoside Thus, the two substrates of this enzyme are UDP- glucose and sterol, whereas its two products are UDP and sterol 3-beta-D- glucoside. This enzyme belongs to the family of glycosyltransferases, specifically the hexosyltransferases. The systematic name of this enzyme class is UDP-glucose:sterol 3-O-beta-D-glucosyltransferase. Other names in common use include UDPG:sterol glucosyltransferase, UDP-glucose-sterol beta- glucosyltransferase, sterol:UDPG glucosyltransferase, UDPG-SGTase, uridine diphosphoglucose-poriferasterol glucosyltransferase, uridine diphosphoglucose- sterol glucosyltransferase, sterol glucosyltransferase, sterol-beta-D- glucosyltransferase, and UDP-glucose-sterol glucosyltransferase.
|
|
Parkeol is a relatively uncommon sterol secondary metabolite found mostly in plants, particularly noted in Butyrospermum parkii (now called Vitellaria paradoxa, or the shea tree). It can be synthesized as a minor product by several oxidosqualene cyclase enzymes, and is the sole product of the enzyme parkeol synthase. Parkeol is the dominant sterol found in the planctomycete Gemmata obscuriglobus, a rare example of a sterol-synthesizing prokaryote. The only other sterol identified in this organism is lanosterol, a key component of the sterol biosynthetic pathway in animals and fungi; this relatively limited sterol repertoire may resemble the early evolution of sterol synthesis, which is ubiquitous in eukaryotes.
|
|
In enzymology, a sterol esterase () is an enzyme that catalyzes the chemical reaction :sterol ester + H2O \rightleftharpoons sterol + fatty acid Thus, the two substrates of this enzyme are sterol ester and H2O, whereas its two products are sterol and fatty acid. This enzyme belongs to the family of hydrolases, specifically those acting on carboxylic ester bonds. The systematic name of this enzyme class is steryl-ester acylhydrolase. Other names in common use include cholesterol esterase, cholesteryl ester synthase, triterpenol esterase, cholesteryl esterase, cholesteryl ester hydrolase, sterol ester hydrolase, cholesterol ester hydrolase, cholesterase, and acylcholesterol lipase.
|
|
The systematic name of this enzyme class is 5α-cholest-7-en-3β-ol,NAD(P)H:oxygen 5-oxidoreductase. Other names in common use include Δ7-sterol Δ5-dehydrogenase, Δ7-sterol 5-desaturase, Δ7-sterol-C5(6)-desaturase, and 5-DES.
|
|
Eburicol, or Obtusifoldienol, also called 24-Methylene-24,25-dihydrolanosterol, is a natural, fungus sterol, which can be demethylated by yeast cytochrome P450 sterol 14alpha-demethylase ERG11.
|
|
C-5 sterol desaturase (also known as sterol C-5 desaturase and C5SD) is an enzyme that is highly conserved among eukaryotes and catalyzes the dehydrogenation of a C-5(6) bond in a sterol intermediate compound as a step in the biosynthesis of major sterols. The precise structure of the enzyme’s substrate varies by species. For example, the human C-5 sterol desaturase (also known as lathosterol oxidase) oxidizes lathosterol, while its ortholog ERG3 in the yeast Saccharomyces cerevisiae oxidizes episterol. The precise structural details of C-5 sterol desaturase substrates vary across eukaryotes.
|
|
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.
|
|
In enzymology, a diacylglycerol-sterol O-acyltransferase () is an enzyme that catalyzes the chemical reaction :1,2-diacyl-sn-glycerol + sterol \rightleftharpoons monoacylglycerol + sterol ester Thus, the two substrates of this enzyme are 1,2-diacyl-sn-glycerol and sterol, whereas its two products are monoacylglycerol 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 1,2-diacyl- sn-glycerol:sterol O-acyltransferase. This enzyme is also called 1,2-diacyl- sn-glycerol:sterol acyl transferase.
|
|
Compound 8 is then catalyzed by sterol C-4 demethylase (E2) and loses a methyl group to produce cycloeucalenol. Subsequent to this, the cyclopropane ring is opened with cycloeucalenol cycloisomerase (E3) to form 10. Compound 10 loses a methyl group and undergoes an allylic isomerization to form Gramisterol 11. This step is catalyzed by sterol C-14 demethylase (E4), sterol Δ14-reductase (E5), and sterol Δ8-Δ7-isomerase (E6).
|
|
Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the SREBF2 gene.
|
|
Dihydrolanosterol, or 24,25-Dihydrolanosterol, also called Lanostenol, is a sterol and the C24-25 hydrogenated products of lanosterol, dihydrolanosterol can be demethylated by mammal or yeast cytochrome P450 sterol 14alpha- demethylase.
|
|
Lichesterol is a sterol made by certain fungi and lichens.
|
|
Fecosterol is a sterol made by certain fungi and lichens.
|
|
Trametenolic acid is an anti-inflammatory sterol isolated from Inonotus obliquus.
|
|
These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.Reviewed in In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity. It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae without having an effect on sterol formation. But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.
|
|
The protein encoded by this gene is an enzyme catalyzing the production of cholesterol from 7-Dehydrocholesterol using NADPH. The DHCR7 gene encodes delta-7-sterol reductase (EC 1.3.1.21), the ultimate enzyme of mammalian sterol biosynthesis that converts 7-dehydrocholesterol (7-DHC) to cholesterol. This enzyme removes the C(7-8) double bond introduced by the sterol delta8-delta7 isomerases.
|
|
643-647 The team joined IBMP in 1989. Using genetics and molecular biology in support of previous methods, cDNA clones encoding biosynthetic enzymes were isolated and characterized for the first time. Mutants affected in sterol biosynthesis, site1 mutant defective in Δ7 sterol-C5-desaturase, sterov mutant overproducing sterolsLaurence Gondet, Roberte Bronner and Pierre Benveniste, « Regulation of sterol content in membranes by subcellular compartmentation of steryl esters accumulating in a sterol-overproducing tobacco mutant », Plant Physiol., 105, 1994, p. 509-518 Daniel Gachotte, Roger Méens and Pierre Benveniste, « Isolation and characterization of an Arabidopsis thaliana cDNA encoding a delta 7-sterol-C-5-desaturase by functional complementation of a defective yeast mutant », The Plant Journal, 8, 1995, p.
|
|
The oxysterol-binding protein (OSBP)-related proteins (ORPs) are a family of lipid transfer proteins (LTPs). Concretely, they constitute a family of sterol and phosphoinositide binding and transfer proteins in eukaryotes that are conserved from yeast to humans. They are lipid-binding proteins implicated in many cellular processes related with oxysterol, including signaling, vesicular trafficking, lipid metabolism, and nonvesicular sterol transport. In yeast cells, some ORPs might function as sterol or lipid transporters though yeast strains lacking ORPs do not have significant defects in sterol transport between the endoplasmic reticulum and the plasma membrane.
|
|
A sterol-sensing domain (SSD) is a protein domain which consists of 180 amino acids forming five transmembrane segments capable of binding sterol groups. This type of domain is present in proteins involved in cholesterol metabolism and signalling.
|
|
ERG4 or Delta(24(24(1)))-sterol reductase or Delta(24(28))-sterol reductase is a enzyme that catalyzes the last step of ergosterol biosynthesis pathway in fungi Saccharomyces cerevisiae (Baker's yeast), which 5,7,22,24(28)-ergostatetraenol converted into ergosterol.
|
|
Branching of the 300x300px FPP is an important metabolic intermediate in the mevalonate pathway that represents a major branch point in terpenoid pathways. FPP is used to form several important classes of compounds in addition to sterols (via squalene), including ubiquinone and dolichols. SQS catalyzes the first committed step in sterol biosynthesis from FPP, and is therefore important for controlling the flux towards sterol vs. non-sterol products.
|
|
This domain, known as a sterol regulatory sequence, directly participates in the regulation of sterol biosynthesis. Sterols are a major class of biomolecule and critical for life. Important sterols in humans include cholesterol and steroid hormones. Discovery of sterol regulatory elements and LDL receptor function led to the subsequent development of statin derived cholesterol medications such as atorvastatin (Lipitor)—the top-selling branded pharmaceutical drug in the world in 2008.
|
|
25-OH acts as an inhibitor of sterol transport mediated by OSBP in vitro.
|
|
Fucosterol is a sterol isolated from algae such as Ecklonia cava or Ecklonia stolonifera.
|
|
The effects of higher serum plant sterol levels are so far not completely understood.
|
|
7-Dehydrositosterol is a sterol which serves as a precursor for sitocalciferol (vitamin D5).
|
|
OSBP is the most extensively studied member of the oxysterol-binding protein (OSBP) related proteins family (ORP). It was first described as the cytoplasmic receptor for 25-hydroxycholesterol, and after more than 20 years it was shown that it's a cholesterol regulated protein in complex with ERK. Now, after the description of the structural basis for sterol sensing and transport, ORP protein family members are known to be essential for sterol signalling and sterol transport functions. Their peculiar structure is characterized by a conserved β-barrel sterol-binding fold with additional domains that can target multiple organelle membranes.
|
|
Episterol is a sterol involved in the biosynthesis of steroids. Episterol is converted from 24-methylenelophenol. Episterol is converted to 5-dehydroepisterol by ERG3, the C-5 sterol desaturase in the yeast. Episterol is also known to be a precursor to ergosterol.
|
|
Emopamil is a calcium channel blocker and a high-affinity ligand of human sterol isomerase.
|
|
Oxysterol-binding protein-related protein 2 is a protein that in humans is encoded by the OSBPL2 gene. This gene encodes a member of the oxysterol- binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although some members contain only the sterol-binding domain. This encoded protein contains only the sterol-binding domain.
|
|
The amino acid sequence that encodes DHCR7 is predicted to contain 475 amino acids, as well as several protein motifs. It contains multiple sterol reductase motifs, as would be expected given its function. It contains a potential sterol-sensing domain (SSD), whose function is unknown but thought to be necessary for binding sterol substrates. It also includes multiple sites of phosphorylation, including potential protein kinase C and tyrosine kinase sites (regulatory enzymes responsible for phosphorylation).
|
|
Sterol esters are a heterogeneous group of chemical compounds. They are created when the hydroxyl group of a sterol and a fatty acid undergo an esterification reaction. They can be found in trace amounts in every cell type but are highly enriched in foam cells and are common components of human skin oil. Plant sterol esters have been shown to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested.
|
|
In yeast, where organelle membranes are closely apposed it has been proposed that ORPs work as sterol transporters, though only a few ORPs actually bind sterols and collectively yeast ORPs are dispensable for sterol transfer in vivo. They are also part of Golgi-to-plasma membrane vesicular trafficking, but their role is not clear yet. In mammalian, ORPs participate as sterol sensors.This sensors regulate the assembly of protein complexes when cholesterol levels fluctuate.
|
|
Delta(14)-sterol reductase is an enzyme that in humans is encoded by the TM7SF2 gene.
|
|
The common class of antifungal drugs known as azoles disrupts the fungal sterol biosynthesis pathway, upstream of C-5 sterol desaturase leading to the accumulation of nontoxic 14α-methylated sterols. C5SD then converts these intermediates into a toxic product. Consequently, in both the pathogenic fungus Candida albicans and model organism S. cerevisiae mutations in the gene encoding C-5 sterol desaturase (ERG3) allow the cell to avoid synthesizing the toxic sterol products and have been shown to confer azole resistance. In at least the case of fluconazole, antifungal resistance due to C5SD inactivation is dependent on the activity of the chaperone protein Hsp90 and the phosphatase calcineurin.
|
|
Fenpropimorph is a morpholine-derived fungicide used in agriculture, primarily on cereal crops such as wheat. It has been reported to disrupt eukaryotic sterol biosynthesis pathways, notably by inhibiting fungal Δ14 reductases. It has also been reported to inhibit mammalian sterol biosynthesis by affecting lanosterol demethylation. Although used in agriculture for pest management purposes, it has been reported to have a strong adverse effect on sterol biosynthesis in higher-plants by inhibiting the cycloeucalenol-obtusifoliol isomerase.
|
|
Lathosterol is a cholesterol-like molecule. Sterol-C5-desaturase-like acts upon it. It is accumulated in lathosterolosis.
|
|
5-Dehydroepisterol is a sterol and an intermediate in steroid biosynthesis, particularly synthesis of brassinosteroids. It is formed from episterol through action of ERG3, the C-5 sterol desaturase in the yeast and is then converted into 24-methylenecholesterol by 7-dehydrocholesterol reductase. Episterol and 5-dehydroepisterol are found in Leishmania.
|
|
Similar bioinformatic analysis has identified a large number of genes in the P. pacifica genome associated with sterol production, which is quite rare among prokaryotes but ubiquitous in eukaryotes. There is evidence that at least some of the sterol- associated genes in P. pacifica derive from horizontal gene transfer from eukaryotes.
|
|
Mutations in this gene may contribute to sterol accumulation and atherosclerosis, and have been observed in patients with sitosterolemia.
|
|
Sterol O-acyltransferase 2, also known as SOAT2, is an enzyme that in humans is encoded by the SOAT2 gene.
|
|
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic- helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes.
|
|
In plants cellular sterol ester synthesis is performed by an enzyme different from mammalian ACAT and yeast ASAT; it is performed by Phospholipid:Sterol Acyltransferase (PSAT). A recent study shows that PSAT is involved in the regulation of the pool of free sterols and the amount of free sterol intermediates in the membranes. It is also described as the only intracellular enzyme discovered that catalyzes an acyl-CoA independent sterol ester formation. PSAT is therefore considered to have a similar physiological function in plant cells as ACAT in animal cells.
|
|
Obtusifoliol is a metabolic intermediate of sterols made by certain fungis, can be converted to Delta8,14-Sterol by enzyme ERG11 (CYP51F1).
|
|
The findings of this study revealed that egro- sterol was not absorbable. This research shaped Schoenheimer's scientific career and research path.
|
|
Cholesterol is a tetracyclic alcohol and a type of sterol. Added to the sterol frame with the alcohol group at position 3 are 2 methyl groups at carbon positions 10 and 13 and a 2-isooctyl group at position 17. The molecule is unsaturated at position 5,6 with an alkene group. The total number of stereocenters is 8.
|
|
Some studies have shown that certain dinoflagellates produce sterols that have the potential to serve as genera-specific biomarkers. Recent work showed that dinoflagellate genera, which formed discrete clusters in the 18S rDNA-based phylogeny, shared similar sterol compositions. This suggested that the sterol compositions of dinoflagellates are explained by the evolutionary history of this lineage.
|
|
Despite a well documented cholesterol lowering effect, there are no data available indicating that functional foods supplemented with plant sterol esters reduce cardiovascular events. They are used in food products such as Benecol. Sterol esters can also be used for the same purpose. These compounds have the same effect to LDL, but they are partially absorbed by the body.
|
|
Some researchers, however, are concerned about diet supplementation with plant sterol esters and draw attention to lack of long-term safety data.
|
|
In addition, genetic infrastructure for sterol biosynthesis is observed in poribacterial genomes, otherwise found almost exclusively in eukaryotes and the planctomycete Gemmata obscuriglobus.
|
|
The activity of SQS is intimately related to the activity of HMG-CoA reductase, which catalyzes the rate-limiting step of the mevalonate pathway. High levels of LDL-derived cholesterol inhibit HMG-CoA reductase activity significantly, since mevalonate is no longer needed for sterol production. However, residual HMG-CoA reductase activity is observed even with very high LDL levels, such that FPP can be made for forming non-sterol products essential for cell growth. To prevent this residual FPP from being used for sterol synthesis when sterols are abundant, SQS activity declines significantly when LDL levels are high.
|
|
In fungi C5SD catalyzes the dehydration of episterol as a step in the synthesis of ergosterol, a sterol that regulates cell membrane fluidity and permeability. In plants such as Arabidopsis thaliana, C-5 sterol desaturase catalyzes the dehydrogenation of episterol and avenasterol in a pathway thought to lead to a variety of membrane components as well as a class of hormones called brassinosteroids.
|
|
Sterols are essential for all eukaryotes. In contrast to animal and fungal cells, which contain only one major sterol, plant cells synthesize an array of sterol mixtures in which sitosterol and stigmasterol predominate. Sitosterol regulates membrane fluidity and permeability in a similar manner to cholesterol in mammalian cell membranes. Plant sterols can also modulate the activity of membrane-bound enzymes.
|
|
In enzymology, a sterol 24-C-methyltransferase () is an enzyme that catalyzes the chemical reaction :S-adenosyl-L-methionine + 5alpha- cholesta-8,24-dien-3beta-ol \rightleftharpoons S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol Thus, the two substrates of this enzyme are S-adenosyl methionine and 5alpha-cholesta-8,24-dien-3beta-ol, whereas its two products are S-adenosylhomocysteine and 24-methylene-5alpha- cholest-8-en-3beta-ol. 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:zymosterol 24-C-methyltransferase. Other names in common use include Delta24-methyltransferase, Delta24-sterol methyltransferase, zymosterol-24-methyltransferase, S-adenosyl-4-methionine:sterol Delta24-methyltransferase, SMT1, 24-sterol C-methyltransferase, S-adenosyl-L- methionine:Delta24(23)-sterol methyltransferase, and phytosterol methyltransferase.
|
|
Sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1, also known as SOAT1, is an enzyme that in humans is encoded by the SOAT1 gene.
|
|
The tuberous roots of Butea superba were found to contain flavonoids and flavonoid glycosides as well as sterol compounds, including β-sitosterol, campesterol and stigmasterol.
|
|
In cells with low levels of sterols, SREBPs are cleaved to a water- soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop.
|
|
In one of his later experiments using sterols, he did discover a small percentage of one sterol, dihydrocholesterol in animal tissue. He investigated this finding using a dog which showed dihydrocholesterol was formed in the tissues. This finding revealed to Schoenheimer that cholesterol was an active metabolite. Schoenheimer and his associates also investigated ergo-sterol, and its behaviour within the bodies of rats, mice, and rabbits.
|
|
Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans. Experimentally, resistance usually arises as a result of mutations in the sterol biosynthesis pathway. Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. Multidrug-resistance (MDR) genes can also play a role in reducing cellular levels of the drug.
|
|
C-5 sterol desaturase couples sterol oxidation to the oxidation of NAD(P)H and the reduction of molecular oxygen. Either NADH or NADPH can be used; in the model plant species Arabidopsis thaliana C-5 sterol desaturase catalyzes the reaction twice as fast with NADH while in S. cerevisiae the enzyme has little preference. The precise details of the reaction have been thought to vary between mammals and yeast. However, the enzymes do share a conserved cluster of histidine residues, which when mutated (in A. thaliana) dramatically reduce or eliminate enzyme activity, suggesting the involvement of a coordinated iron cation in the mechanism.
|
|
In rabbits, liver cells sense the reduced levels of liver cholesterol and seek to compensate by synthesizing LDL receptors to draw cholesterol out of the circulation. This is accomplished via proteases that cleave membrane-bound sterol regulatory element binding proteins, which then migrate to the nucleus and bind to the sterol response elements. The sterol response elements then facilitate increased transcription of various other proteins, most notably, LDL receptor. The LDL receptor is transported to the liver cell membrane and binds to passing LDL and VLDL particles, mediating their uptake into the liver, where the cholesterol is reprocessed into bile salts and other byproducts.
|
|
In enzymology, a Delta24(241)-sterol reductase () is an enzyme that catalyzes the chemical reaction :ergosterol + NADP+ \rightleftharpoons ergosta-5,7,22,24(241)-tetraen-3beta-ol + NADPH + H+ Thus, the two substrates of this enzyme are ergosterol and NADP+, whereas its 3 products are ergosta-5,7,22,24(241)-tetraen-3beta-ol, NADPH, and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is ergosterol:NADP+ Delta24(241)-oxidoreductase. Other names in common use include sterol Delta24(28)-methylene reductase, and sterol Delta24(28)-reductase. This enzyme participates in biosynthesis of steroids.
|
|
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.
|
|
"Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. II. Purification and characterization.". The Journal of Biological Chemistry. Retrieved November 29, 2012.
|
|
Penicillium westlingii is a species of fungus in the genus Penicillium which was isolated from soil near Poznan in Poland.UniProt Penicillium westlingii produces citrinin and sterol.
|
|
As azole antifungals all act at the same point in the sterol pathway, resistant isolates are normally cross-resistant to all members of the azole family.
|
|
Known substrates include sterol regulatory element- binding protein (SREBP)-1, SREBP-2 and forms of the transcriptional activator ATF6. This enzyme belongs to the peptidase family M50.
|
|
A sterol isolated from the species was reported as a rare example of a molecule capable of reversing multidrug efflux-mediated fungal resistance to the drug fluconazole.
|
|
This interaction catalyzes the development of an irreversible matrix of glycoalkaloid-sterol complexes (figure 2, part 4). In this way, the sterols from the external membrane are immobilized and membrane budding will arise. Tubular structures are formed, because of the structure of tomatine (figure 2, part 6).Keukens, Erik AJ, et al; Dual specificity of sterol-mediated glycoalkaloid induced membrane disruption; Biochimica et Biophysica Acta (BBA) - Biomembranes 1110.2, 1992; 127-136.
|
|
This is the notion Schoenheimer investigated in his experiments. One of his experiments involved administering two different diets to a group of rabbits. Rabbits are sensitive to a diet which includes cholesterol, and their bodily responses particularly that of the aorta demonstrates a change that similarly resembles the Human atherosclerosis. In the experiment one diet involved a large amount of sito- sterol, which is a type of plant sterol.
|
|
Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a protein that in humans is encoded by the SREBF1 gene. This gene is located within the Smith–Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene. The isoforms are SREBP-1a and SREBP-1c (the latter also called ADD-1).
|
|
In yeast, Osh4 is an OSBP homologue the crystal structure of which, obtained in both the sterol-bound and unbound states, showed a soluble β-barrel protein with a hydrophilic external surface and a hydrophobic pocket that can carry a single sterol molecule. Seven OSBP homologues (OSH proteins) have been identified in Saccharomyces cerevisiae, in which their role has been suggested to be more relevant to sterol organization in the PM, rather than sterol trafficking from ER. Furthermore, Stefan et al. showed that OSH proteins control PI4P metabolism via the Sac1 Phosphatidylinositol (PI) 4-phosphatase. They also proposed a mechanism for Sac1 regulation: high Phosphatidylinositol 4-phosphate (PI4P) levels on the plasma membrane recruit Osh3 at PM-ER contact sites through its pleckstrin homology (PH) domain; Osh3 is now active and can interact with the ER-resident VAP proteins Scs2/Scs22 through its FFAT motif (two phenylalanines on an acidic tract), ultimately activating ER-localized Sac1 to reduce PI levels.
|
|
Cholestenol is a sterol that has been found in the skins of rats. It can be converted to cholesterol in mammals. Delta-7-cholestenol is also known as lathosterol.
|
|
The enzyme’s genetic expression is regulated by sterol regulatory element binding protein (SREBP-2), a molecule which also regulates the expression of other enzymes in the cholesterol biosynthesis pathway.
|
|
Its expression is induced by decreased sterol concentrations via sterol regulatory binding proteins (SREBP). There is also evidence that its activity may be regulated by tissue specific transcription, and alternative splicing. As outlined above, the enzyme DHCR7 catalyzes the reduction of 7DHC to cholesterol, as well as the reduction of 7-dehydrodesmosterol to desmosterol. It requires NADPH as a cofactor for this reduction, and may involve the activity of cytochrome-P450 oxidoreductase.
|
|
A feature unique to kpangnan butter is its high stigmasterol content (around 45% of the sterol content). Stigmasterol is the sterol unsaturated vegetable fat usually found in plant parts such as calabar bean, soybean oil, rapeseed oil, and cocoa butter. Stigmasterol is used as a base material in the production of synthetic progesterone, but has other interesting properties. Research shows that stigmasterol can reduce the risk of certain cancers, including ovarian cancer.
|
|
Zaragozic acids are potent inhibitors of S. cervisiae, fungal and mammalian squalene synthase and therefore inhibitors of sterol synthesis. Squalene synthase is the first committed enzyme in sterol synthesis, catalyzing the reductive condensation of farnesyl pyrophosphate to form squalene. As a squalene synthase inhibitor, zaragozic acid produces lower plasma cholesterol levels in primates. Treatment of rats with zaragozic acid A caused an increase in hepatic low density lipoprotein (LDL) receptor mRNA levels.
|
|
The VASt domain is predominantly associated with lipid binding domains, such as GRAM. It is most likely to function in binding large hydrophobic ligands and may be specific for sterol.
|
|
Additional lines of evidence for the existence of this clade have been found. These include the presence of membrane coat-like proteins, tubulin, sterol synthesis, and the presence of condensed DNA.
|
|
Non-specific lipid-transfer protein also known as sterol carrier protein 2 (SCP-2) or propanoyl-CoA C-acyltransferase is a protein that in humans is encoded by the SCP2 gene.
|
|
Plant sterol esters used for dietary supplements are made from phytosterols and fatty acids also derived from plants. They are added to certain oil-containing products like margarine, milk, or yogurt to make functional foods for controlling cholesterol levels. Studies have indicated that consumption of about 2 grams per day of phytosterol esters provides a reduction in LDL cholesterol of around 10%. Sterol esters are added to certain Unilever products under the brand name Becel/Flora.
|
|
Dinosterol is a type of steroid produced by several genera of dinoflagellates. It is a 4α-methyl sterol (4α,23,24-trimethyl-5α-cholest-22E-en-3β-ol), a derivative of dinosterane, rarely found in other classes of protists. This sterol and others have been considered as class-specific, being biomarkers for dinoflagellates, although dinosterol is produced in minor amounts by a small number of other phytoplankton, such as the marine diatom Navicula speciosa. and Prymnesiophytes of the genus Pavlova.
|
|
Cholesterol (from the Ancient Greek chole- (bile) and stereos (solid), followed by the chemical suffix -ol for an alcohol) is an organic molecule. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membranes. Cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Cholesterol is the principal sterol synthesized by all animals.
|
|
USA, 88,1991, p. 6926-6930 Between 1963 and 1987, sterol biosynthesis was studied by radiochemical methods, enzymology and the use of inhibitors, analogues of transition states involved in the catalysis of target enzymes.Alain Rahier, Jean-Claude Genot, Francis Schuber, Pierre Benveniste and Acharan Narula, « Inhibition of S-adenosyl-L-methionine sterol-C-24-methyltransferase by analogues of a carbocationic ion high energy intermediate. Structure activity relationships for C-25 heteroatoms (N, As, S) substituted triterpenoid derivatives », J. Biol. Chem.
|
|
In animals and archaea, the mevalonate pathway produces these compounds from acetyl-CoA, while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates. One important reaction that uses these activated isoprene donors is sterol biosynthesis. Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol. Lanosterol can then be converted into other sterol such as cholesterol and ergosterol.
|
|
4,4'-Dihydroxybenzophenone is an organic compound with the formula (HOC6H4)2CO. This off-white solid is a precursor to or a degradation product of diverse commercial materials. It is a potential endocrine disruptor.Eddine, Ali Nasser; von Kries, Jens P.; Podust, Mikhail V.; Warrier, Thulasi; Kaufmann, Stefan H. E.; Podust, Larissa M. "X-ray Structure of 4, 4 '- Dihydroxybenzophenone Mimicking Sterol Substrate in the Active Site of Sterol 14a -Demethylase (CYP51)" Journal of Biological Chemistry (2008), 283, pp. 15152-15159.
|
|
Metabolism and homeostasis of fatty acid synthase is transcriptionally regulated by Upstream Stimulatory Factors (USF1 and USF2) and sterol regulatory element binding protein-1c (SREBP-1c) in response to feeding/insulin in living animals. Although liver X receptor (LXRs) modulate the expression of sterol regulatory element binding protein-1c (SREBP-1c) in feeding, regulation of FAS by SREBP-1c is USF-dependent. Acylphloroglucinols isolated from the fern Dryopteris crassirhizoma show a fatty acid synthase inhibitory activity.
|
|
Because the EQVSHHPP sequence is crucial for PI4P binding to the ORD, but not for sterol binding, it has been proposed that PI4P transport is a common function of Osh/ORP proteins.
|
|
Agosterol A is a bio-active sterol which may have applications in removing multi-drug resistance in various cancers. It was first isolated from marine sponge but has also been produced synthetically.
|
|
In 1987, the division in sterol requiring and not requiring changed with the addition of a third order, Anaeroplasmatales, taking into account that dependence on anaerobic growth conditions is an important characteristic.
|
|
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating is an enzyme that in humans is encoded by the NSDHL gene. This enzyme is localized in the endoplasmic reticulum and is involved in cholesterol biosynthesis.
|
|
It contains the EQVSHHPP sequence. It has an hydrophobic pocket that binds a sterol and also contains multiple membrane binding surfaces which permit the protein to have the ability to cause liposome aggregation.
|
|
Sterol carrier proteins (also known as nonspecific lipid transfer proteins) is a family of proteins that transfer steroids and probably also phospholipids and gangliosides between cellular membranes. These proteins are different from plant nonspecific lipid transfer proteins but structurally similar to small proteins of unknown function from Thermus thermophilus. This domain is involved in binding sterols. The human sterol carrier protein 2 (SCP2) is a basic protein that is believed to participate in the intracellular transport of cholesterol and various other lipids.
|
|
Oxysterol-binding protein-related protein 1 is a protein that in humans is encoded by the OSBPL1A gene. This gene encodes a member of the oxysterol- binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although some members contain only the sterol-binding domain. Transcript variants derived from alternative promoter usage and/or alternative splicing exist; they encode different isoforms.
|
|
The proteins encoded by this gene are transcription factors that bind to a sequence in the promoter of different genes, called sterol regulatory element-1 (SRE1). This element is a decamer (oligomer with ten subunits) flanking the LDL receptor gene and other genes involved in, for instance, sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1.
|
|
Several variations on this basic structure exist, including backbones such as sphingosine in the sphingomyelin, and hydrophilic groups such as phosphate as in phospholipids. Steroids such as sterol are another major class of lipids.
|
|
Inhibitors of intestinal sterol absorption, such as ezetimibe, function by decreasing the absorption of cholesterol in the GI tract by targeting NPC1L1, a transport protein in the gastrointestinal wall. This results in decreased LDL cholesterol.
|
|
This enzymatic activity is performed by CYP8B1. Other names used include 7alpha-hydroxy-4-cholesten-3-one 12alpha-monooxygenase, CYP12, sterol 12alpha-hydroxylase (ambiguous), and HCO 12alpha-hydroxylase. This enzyme participates in ppar signaling pathway.
|
|
Isofucosterol, or 28-Isofucosterol, also called Δ-5-Avenasterol, is the E–Z isomer of Fucosterol and position isomer of Δ-7-Avenasterol. Isofucosterol is a natural, stigmastane-type sterol, mainly distributed in marine sponge.
|
|
Transcription of the reductase gene is enhanced by the sterol regulatory element binding protein (SREBP). This protein binds to the sterol regulatory element (SRE), located on the 5' end of the reductase gene after controlled proteolytic processing. When SREBP is inactive, it is bound to the ER or nuclear membrane with another protein called SREBP cleavage-activating protein (SCAP). SCAP senses low cholesterol concentration and transports SREBP to the Golgi membrane where a consecutive proteolysis by S1P and S2P cleaves SREBP into an active nuclear form, nSREBP.
|
|
Unlike LDLR, VLDLR does not exhibit any feedback mechanism, and hence intracellular lipoproteins are incapable of regulating it. This phenomenon is due to a difference in the sterol regulatory element-1 (SRE-1) of VLDLR. Normal SRE-1 sequences, like those found in LDLR, are characterized by two repeats of the codon CAC separated by two intervening C nucleotides (5’-CACCCCAC-3’). The sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor, targets the CAC repeats of SRE-1 to regulate the protein’s transcription.
|
|
OSBP is thought to be an essential scaffolding compound of the protein complex that regulates the activation state of the ERK protein. OSBP also acts as a sterol-dependant scaffold for the JAK2 and STAT3 proteins.
|
|
Like most boletes of genus Tylopilus, the mushroom is inedible due to its bitter taste. A number of natural products have been identified from the fruit bodies, including unique chemical derivatives of ergosterol, a fungal sterol.
|
|
Miconazole inhibits the fungal enzyme 14α-sterol demethylase, resulting in a reduced production of ergosterol. In addition to its antifungal actions, miconazole, similarly to ketoconazole, is known to act as an antagonist of the glucocorticoid receptor.
|
|
The FDA has approved the following claim for phytosterols: For plant sterol esters: (i) Foods containing at least 0.65 g per serving of plant sterol esters, eaten twice a day with meals for a daily total intake of at least 1.3 g, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease. A serving of [name of the food] supplies ___grams of vegetable oil sterol esters. For plant stanol esters: (i) Foods containing at least 1.7 g per serving of plant stanol esters, eaten twice a day with meals for a total daily intake of at least 3.4 g, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease. A serving of [name of the food] supplies ___grams of plant stanol esters.
|
|
When treating SLOS, a recurring issue is whether or not the intellectual and behavioural deficits are due to fixed developmental problems (i.e. fixed brain malformations), or due to ongoing abnormal sterol levels that interrupt the normal function of the brain and other tissues. If the latter is true, then treatments which change the sterol levels and ratios, particularly in the brain, will likely improve the developmental outcome of the patient. However, if the former is true, then treatment is likely to help only with symptoms and not with specific developmental deficits.
|
|
SQS regulation occurs primarily at the level of SQS gene transcription. The sterol regulatory element binding protein (SREBP) class of transcription factors is central to regulating genes involved in cholesterol homeostasis, and is important for controlling levels of SQS transcription. When sterol levels are low, an inactive form of SREBP is cleaved to form the active transcription factor, which moves to the nucleus to induce transcription of the SQS gene. Of the three known SREBP transcription factors, only SREBP-1a and SREBP-2 activate SQS gene transcription in transgenic mouse livers.
|
|
Volemitol Fruit bodies contains a unique sterol molecule called volemolide, a derivative of the common fungal sterol ergosterol that may have application in fungal chemotaxonomy. A 2001 study identified a further nine sterols, three of which were previously unknown to science. According to the authors, these types of highly oxygenated compounds—similar to sterols found in marine soft coral and sponges—are rare in fungi. The mushroom also contains volemitol (D-glycero-D-mannoheptitol), a seven-carbon sugar alcohol first isolated from the species by the French scientist Émile Bourquelot in 1889.
|
|
Sterol O-acyltransferase (also called Acyl-CoA cholesterol acyltransferase, Acyl-CoA cholesterin acyltransferase or simply ACAT) is an intracellular protein located in the endoplasmic reticulum that forms cholesteryl esters from cholesterol. Sterol O-acyltransferase catalyzes the chemical reaction: :acyl-CoA + cholesterol \rightleftharpoons CoA + cholesterol ester Thus, the two substrates of this enzyme are acyl-CoA and cholesterol, whereas its two products are CoA and cholesteryl ester. This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups, the membrane-bound O-acyltransferases. This enzyme participates in bile acid biosynthesis.
|
|
SREBF1 (sterol regulatory element-binding transcription factor 1) is a transcription factor synthesized as an inactive precursor protein inserted into the endoplasmic reticulum (ER) membrane by two membrane-spanning helices. Also anchored in the ER membrane is SCAP (SREBF-cleavage activating protein), which binds SREBF1. The SREBF1-SCAP complex is retained in the ER membrane by INSIG1 (insulin- induced gene 1 protein). When sterol levels are depleted, INSIG1 releases SCAP and the SREBF1-SCAP complex can be sorted into COPII-coated transport vesicles that are exported to the Golgi.
|
|
Basic helix-loop-helix leucine zipper transcription factors are, as their name indicates, transcription factors containing both Basic helix-loop-helix and leucine zipper motifs. Examples include Microphthalmia-associated transcription factor and Sterol regulatory element binding protein (SREBP).
|
|
Cerevisterol inhibits the eukaryotic enzyme DNA polymerase alpha, and it is also a potent inhibitor of NF-kappa B activation. The sterol is cytotoxic to mouse P388 leukemia cells and A549 human alveolar epithelial cells grown in culture.
|
|
Lipin-1 has phosphatidate phosphatase activity. The nuclear localization of Lipin 1 is regulated by the mammalian Target Of Rapamycin protein kinase and links mTORC1 activity to the regulation of Sterol regulatory element-binding proteins (SREBP)-dependent gene transcription.
|
|
Trametes versicolor contains polysaccharides under basic research, including the protein-bound PSP and β-1,3 and β-1,4 glucans. The lipid fraction contains the lanostane-type tetracyclic triterpenoid sterol ergosta-7,22,dien-3β-ol as well as fungisterol and β-sitosterol.
|
|
Arjmandi received his Ph.D. From Kansas State University, where he studied the effect of soluble fiber on sterol synthesis and later completed his postdoctoral work in the area of estrogen and bone physiology at the University of Texas Health Science Center.
|
|
Both seed and pulp oil also contain considerable amounts of plant sterols (12-23 g/kg and 10-29 g/kg of oil, respectively). Beta-sitosterol is the major sterol compound throughout the berry which constitutes 57-83% of total sterols.
|
|
The most characteristic biochemical indicator of SLOS is an increased concentration of 7DHC (reduced cholesterol levels are also typical, but appear in other disorders as well). Thus, prenatally, SLOS is diagnosed upon finding an elevated 7DHC:total sterol ratio in fetal tissues, or increased levels of 7DHC in amniotic fluid. The 7DHC:total sterol ratio can be measured at 11–12 weeks of gestation by chorionic villus sampling, and elevated 7DHC in amniotic fluid can be measured by 13 weeks. Furthermore, if parental mutations are known, DNA testing of amniotic fluid or chorionic villus samples may be performed.
|
|
This pathway plays a key role in multiple cellular processes by synthesizing sterol isoprenoids, such as cholesterol, and non-sterol isoprenoids, such as dolichol, heme A, tRNA isopentenyltransferase, and ubiquinone. This enzyme belongs to the family of lyases, specifically the carboxy-lyases, which cleave carbon-carbon bonds. The systematic name of this enzyme class is ATP:(R)-5-diphosphomevalonate carboxy-lyase (adding ATP isopentenyl- diphosphate-forming). Other names in common use include pyrophosphomevalonate decarboxylase, mevalonate-5-pyrophosphate decarboxylase, pyrophosphomevalonic acid decarboxylase, 5-pyrophosphomevalonate decarboxylase, mevalonate 5-diphosphate decarboxylase, and ATP:(R)-5-diphosphomevalonate carboxy-lyase (dehydrating).
|
|
The results show for the first time that in Arabidopsis and all higher plants there are two gene subfamilies: SMT1 and SMT2 coding for methyltransferases involved in the methylation reactions leading to the formation of 24-methyl and 24-ethyl cholesterols.Bouvier-Navé, P., Husselstein, T. et Benveniste P., « Two families of sterol methyltransferases are involved in the first and the second methylation steps of plant sterol biosynthesis. », Eur J Biochem, 1998, 256, p. 88-96 The overexpression or cosuppression of SMT2 in tobacco or Arabidopsis lines has a profound impact on the relative proportions of 24-methyl and 24-ethyl cholesterol.
|
|
The NPC1L1 protein which sits on the luminal side of the enterocyte is responsible for sterol absorption. Its counterpart, the ABCG5/G8 ATP Binding Cassette protein which also sits on the luminal side of the enterocyte, and on the bile canaliculi side of the hepatocyte, is responsible for sterol efflux. Variations in each of these proteins causes variation in absorption and efflux of dietary and biliary sterols - both cholesterol and plant sterols. Although studies in humans have shown that consumption of phytosterols may reduce LDL levels, evidence to recommend them as a treatment for hypercholesterolemia is insufficient.
|
|
The most important fatty acids in seed oil are palmitic acid, oleic acid and linoleic acid, while the main sterol is β-sitosterol. An extract of the stem bark proved to be toxic to microfilariae of Onchocerca volvulus, the cause of river blindness.
|
|
The debate regarding sterol vs. stanol safety is centered on their differing intestinal absorption and resulting plasma concentrations. Phytostanols have a lower estimated intestinal absorption rate (0.02 - 0.3%) than phytosterols (0.4 - 5%) and consequently blood phytostanol concentration is generally lower than phytosterol concentration.
|
|
This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol- binding domain.
|
|
They have been shown to secrete 25-hydroxycholesterol, a sterol that can be converted to testosterone by Leydig cells. Their presence is necessary for the normal development and function of the Leydig cells, which are the testosterone-producing cells of the testis.
|
|
Unlike imidazole- and triazole-class antifungals, abafungin directly impairs the fungal cell membrane. In addition, abafungin inhibits the enzyme sterol 24-C-methyltransferase, modifying the composition of the fungal membrane. Abafungin has antibiotic activity against gram- positive bacteria as well as sporicidal activity.
|
|
Such accumulation bodies are associated with increased sterol concentrations. Vegetative cells are described as irregularly shaped and containing sterols characterized as (E)-24-propylidenecholesterol, stigmasterol, sitosterol, cholesterol, (24R)-24-propylcholesterol with trace amounts of 24-methylenecholesterol, crinosterol, clerosterol, campesterol, dihydrobrassicasterol, and 24-isopropylcholesterol.
|
|
Wang X, Sato R, Brown MS, Hua X, Goldstein JL. (April 8, 1994). "SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.". Cell. Retrieved November 29, 2012.Wang X, Briggs MR, Hua X, Yokoyama C, Goldstein JL, Brown MS. (June 5, 1993).
|
|
Cycloartenol is an important triterpenoid of the sterol class which is found in plants. It is the starting point for the synthesis of almost all plant steroids, making them chemically distinct from the steroids of fungi and animals which are instead produced from lanosterol.
|
|
Insulin is the principal signal for increased transcription, operating mainly by way of a transcription factor called sterol regulatory element binding protein-1c (SREBP1c) except in the liver. This occurs within an hour after a rise in insulin levels, as after a carbohydrate meal.
|
|
Steryl-sulfatase is also known as arylsulfatase, steroid sulfatase, sterol sulfatase, dehydroepiandrosterone sulfate sulfatase, arylsulfatase C, steroid 3-sulfatase, steroid sulfate sulfohydrolase, dehydroepiandrosterone sulfatase, pregnenolone sulfatase, phenolic steroid sulfatase, 3-beta-hydroxysteroid sulfate sulfatase, as well as by its systematic name steryl-sulfate sulfohydrolase.
|
|
Lipids movement between cellular membranes. As part of the Lipid Transfer proteins (LTPs) family, ORPs have different and variate functions. This functions include signaling, vesicular trafficking, lipid metabolism and nonvesicular sterol transport. ORPs have been studied in many organisms cells as human cells or yeast.
|
|
First, diplopterol is synthesized when water quenches the C-22 carbocation formed during polycyclization. This indicates that hopanoids can be made without molecular oxygen and could have served as a sterol surrogate before the atmosphere accumulated oxygen, which reacts with squalene in a reaction catalyzed by squalene monooxygenase during sterol biosynthesis. Furthermore, squalene binds to squalene-hopene cyclases in a low-energy, all-chair conformation while oxidosqualene is cyclized in a more strained, chair-boat-chair-boat conformation. Squalene-hopene cyclases also display more substrate promiscuity in that they cyclize oxidosqualene in vitro, causing some scientists to hypothesize that they are evolutionary predecessors to oxidosqualene cyclases.
|
|
It was assumed also that there would only small chemical changes were necessary when modifying these compounds to suit specific needs. Previous cholesterol-balance studies indicated that under specific conditions, animals could possess the ability to form cholesterol, as it has been discovered that sometimes negative balances are present in metabolic studies, wherein more sterol is excreted than consumed. These observations did not demonstrate whether cholesterol present in the animal body was due to synthesis or whether it had all actually come from vegetable food. The transformation of plant sterols into cholesterol within the body of an animal requires the sterol to be absorbable.
|
|
This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms.
|
|
The bacterial mass increases and cecal bacterial activity increases. # The enteric loss of bile acids results in increased synthesis of bile acids from cholesterol which in turn reduces body cholesterol. The fibers that are most effective in influencing sterol metabolism (e.g. pectin) are fermented in the colon.
|
|
Cooked sweetcorn releases increased levels of ferulic acid. As plant sterol esters, this compound is naturally found in rice bran oil, a popular cooking oil in several Asian countries. Ferulic acid glucoside can be found in commercial breads containing flaxseed. Rye bread contains ferulic acid dehydrodimers.
|
|
This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Several transcript variants encoding different isoforms have been identified.
|
|
Finally, VLDLR is affected by the presence of apoE and LDLR. The presence of apoE is required for VLDLR expression regulation, while the absence of LDLR alters the sterol-regulatory-element-1-like sequences of VLDLR to make them functional in only heart and skeletal muscle.
|
|
The results obtained show that the sterov mutation affects the activity of Hydroxy-Methyl-Glutaryl-CoA reductase, which is strongly stimulated in the mutant. More recent work highlights the importance of sterol esterification in this mutant. In this mutant, excess sterols are found in the form of sterol esters which accumulate dramatically in lipid globules. The work carried out shows that the plants have the originality of carrying out the cellular esterification of sterols by an enzyme (of LCAT type, lecithin cholesterol acyltransferase) different from that (of ACAT type, acylCoA cholesterol acyltransferase) operating in animals and fungi.Bouvier- Navé, P., Benveniste, P., Oelkers, P., Sturley, S.L. et Schaller, H., « Expression in yeast and tobacco of plant cDNAs encoding acyl CoA: diacylglycerol acyltransferase », Eur J Biochem, 267, 2000, p. 85-96Banas A, Carlsson AS, Huang B, Lenman M, Banas W, Lee M, Noiriel A, Benveniste P, Schaller H, Bouvier-Nave P, Stymne S., « Cellular Sterol Ester Synthesis in Plants Is Performed by an Enzyme (Phospholipid:Sterol Acyltransferase) Different from the Yeast and Mammalian Acyl-CoA:Sterol Acyltransferases », J Biol Chem.
|
|
Dinosterols show similar abundances as dinocysts. Other studies found a nonlinear or did not find a direct link between dinocyst abundances and sterol concentrations. Dinosterol has been used as indicator for dinoflagellate production in the Cariaco Basin. Hydrogen isotope ratios in dinosterols can serve to reconstruct salinity semi- quantitatively.
|
|
Sterols of plants are called phytosterols and sterols of animals are called zoosterols. The most important zoosterol is cholesterol; notable phytosterols include campesterol, sitosterol, and stigmasterol. Ergosterol is a sterol present in the cell membrane of fungi, where it serves a role similar to cholesterol in animal cells.
|
|
Tetrahymanol is a pentacyclic triterpenoid molecule. The triterpenoids are a class of molecules found in both bacteria and eukaryotes, which largely make hopanols and sterols, respectively. The structures of these three classes of molecules are shown below. Cholesterol and diploptene are used as model sterol and hopanol structures, respectively.
|
|
The best known sterol is cholesterol, which is found in humans. Cholesterol also occurs naturally in other eukaryote cell membranes. Sterols have a hydrophobic four-membered fused ring rigid structure, and a small polar head group. Cholesterol is bio-synthesised from mevalonate via a squalene cyclisation of terpenoids.
|
|
Using this approach, lipids may be divided into eight categories: fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, and polyketides (derived from condensation of ketoacyl subunits); and sterol lipids and prenol lipids (derived from condensation of isoprene subunits). Although the term "lipid" is sometimes used as a synonym for fats, fats are a subgroup of lipids called triglycerides. Lipids also encompass molecules such as fatty acids and their derivatives (including tri-, di-, monoglycerides, and phospholipids), as well as other sterol-containing metabolites such as cholesterol. Although humans and other mammals use various biosynthetic pathways both to break down and to synthesize lipids, some essential lipids can't be made this way and must be obtained from the diet.
|
|
350x350px The enzyme responsible for making isoarborinol may represent the evolutionary link between the hopanol-producing enzymes in bacteria and the sterol-producing enzymes in eukaryotes. These enzymes are part of the class of terpene cyclases, which cyclize either squalene or oxidosqualene into four- or five-membered ring compounds through pathways that proceed through different structural conformations (all-chair or chair-boat-chair). Each terpene cyclase uses a different combination of these aspects to produce the final polycyclic triterpenoid compound, leading to great variety in the pathways of polycyclic triterpenoid production. Squalene- hopene cyclase (SHC) synthesizes hopanols and is generally assumed to have evolved before the sterol-producing enzyme oxidosqualene cyclase (OSC).
|
|
ERG5 or Sterol 22-desaturase is a cytochrome P450 enzyme in the ergosterol biosynthesis pathway of fungi Saccharomyces cerevisiae (Baker's yeast, a model organism), with the CYP Symbol CYP61A1. CYP61A1 is one of only three P450 enzyme found in baker's yeast, the other two are CYP51F1 and CYP56A1. The ortholog in Schizosaccharomyces pombe (fission yeast, the second sequenced model fungi), was named CYP61A3 for historical reasons, and is only one of two P450 enzyme found with CYP51F1. ERG5 catalyzes the C22-C23 double bond formation on the sterol side chain of ergostatrienol to convert it into ergostatetraenol, then the C24 double bond of ergostatetrenol will be hydrogenation reduced into ergosterol by ERG4.
|
|
Cerevisterol (5α-ergosta-7,22-diene-3β,5,6β-triol) is a sterol. Originally described in the 1930s from the yeast Saccharomyces cerevisiae, it has since been found in several other fungi and, recently, in deep water coral. Cerevisterol has some in vitro bioactive properties, including cytotoxicity to some mammalian cell lines.
|
|
Plant sterol levels in the blood have been shown to be positively, negatively or not associated with CVD risk, depending on the study population investigated. The link between plant sterols and CVD or CHD risk is complicated because phytosterol levels reflect cholesterol absorption. (See Phytosterols as a marker for cholesterol absorption).
|
|
The regulation of expression of AO is still not completely known, though some studies have shown that the AOX1 gene is regulated by the Nrf2 pathway. Some known inhibitors of AO are sterol and phenol compounds, like estradiol. Others include amsacrine, 6,6'-azopurine, chlorpromazine, cimetidine, cyanide, diethylstilbestrol, genestein, isovanillin, and methadone.
|
|
The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or serine. Phospholipids are a key component of all cell membranes. They can form lipid bilayers because of their amphiphilic characteristic. In eukaryotes, cell membranes also contain another class of lipid, sterol, interspersed among the phospholipids.
|
|
This enzyme is one of C-5 sterol desaturases, belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as one donor, and the other dehydrogenated.
|
|
ABCG5 and ABCG8 genes encode for two proteins sterolin-1 and -2, respectively. Sterolin-1 and –2 are two ‘half’ adenosine triphosphate binding (ATP) cassette (ABC) transporters which found to be indispensable for the regulation of sterol absorption and excretion. Mutations in either genes result in a lipid disorder, sitosterolemia.
|
|
Membrane-bound transcription factor site-1 protease, or site-1 protease (S1P) for short, also known as subtilisin/kexin-isozyme 1 (SKI-1), is an enzyme (EC 3.4.21.112) that in humans is encoded by the MBTPS1 gene. S1P cleaves the endoplasmic reticulum loop of sterol regulatory element-binding protein (SREBP) transcription factors.
|
|
A. Keys et al., Serum cholesterol response to changes in the diet. IV. Particular saturated fatty acids in the diet, Metabolism 14, 776-787 (1965) More recently, products were introduced under the "Pro-activ" sub-brand. These products are based on the effects of plant sterols and sterol esters on blood cholesterol lowering.
|
|
The following was concluded based on ethanol's ability to induce non-lamellar phases: #Ethanol does induce non-lamellar phases (non-bilayer) but this process is concentration-dependent. On average the bilayers is preserved at approximately less than 10 mol%. #Ethanol prefers to bond in the hydrophilic region near phosphate groups which could be contributed to its amphiphilic character. #The effects of ethanol can be reversed or hindered in the presence of cholesterol (sterol compounds) #It may be necessary to perform a future study to compare the maximum amount of cholesterol (30 mol%) obtained in the NNR study to varied concentrations of ethanol as depicted in the AMDS study to see if ethanol is still hindered in the presence of sterol compounds.
|
|
In enzymology, a propionyl-CoA C2-trimethyltridecanoyltransferase () is an enzyme that catalyzes the chemical reaction :4,8,12-trimethyltridecanoyl-CoA + propanoyl-CoA \rightleftharpoons 3-oxopristanoyl-CoA + CoA Thus, the two substrates of this enzyme are 4,8,12-trimethyltridecanoyl-CoA and propanoyl- CoA, whereas its two products are 3-oxopristanoyl-CoA and CoA. 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 4,8,12-trimethyltridecanoyl-CoA:propanoyl-CoA C2-4,8,12-trimethyltridecanoyltransferase. Other names in common use include 3-oxopristanoyl-CoA hydrolase, 3-oxopristanoyl-CoA thiolase, peroxisome sterol carrier protein thiolase, sterol carrier protein, oxopristanoyl-CoA thiolase, peroxisomal 3-oxoacyl coenzyme A thiolase, SCPx, 4,8,12-trimethyltridecanoyl- CoA:propanoyl-CoA, and 2-C-4,8,12-trimethyltridecanoyltransferase.
|
|
Under normal circumstances, a western diet contains almost equal amounts of cholesterol and noncholesterol sterols (such as plant sterols sitosterol, campesterol, and brassicasterol). However, only about 55% of total dietary cholesterol is absorbed and retained while almost none of the noncholesterol sterols are retained since the small amount of dietary non-cholesterols that do enter the body are rapidly excreted by the liver into bile, almost unchanged. Sterolins are likely involved both in the selective transport of dietary cholesterol in and out of enterocytes and in selective sterol excretion by the liver into bile, as evidenced by the consequences when it is deficient or over expressed. The exact mechanism(s) whereby ABCG5/ABCG8 exert their effects on sterol metabolism has not yet been clarified.
|
|
The predominant sterol in fungal cell membranes is ergosterol. Sterols are steroids in which one of the hydrogen atoms is substituted with a hydroxyl group, at position 3 in the carbon chain. They have in common with steroids the same fused four- ring core structure. Steroids have different biological roles as hormones and signaling molecules.
|
|
Brassicasterol (24-methyl cholest-5,22-dien-3β-ol) is a 28-carbon sterol synthesised by several unicellular algae (phytoplankton) and some terrestrial plants, like rape. This compound has frequently been used as a biomarker for the presence of (marine) algal matter in the environment, and is one of the ingredients for E number E499.
|
|
KIAA1958 is located on the long arm of chromosome 9 (9.q32) in humans on the plus strand from 115249248 to 115427597. Its mRNA has 2683 bp. The gene has these neighbors on chromosome 9: KIAA1958 gene neighbors HSDL2: Hydroxysteroid dehydrogenase-like protein 2 plays a role in nucleotide binding, oxidoreductase activity, and sterol binding.
|
|
The last methyl group is removed by sterol demethylase (E7) to form episterol 12. Episterol 12 is methylated by SAM to produce a second carbocation, which loses a proton to yield 13. This step is catalyzed by 24-methylenesterol C-methyltransferase (E8). Compound 13 now undergoes reduction by NADPH and modifications in the β-ring to form β-sitosterol.
|
|
C-5 sterol desaturase catalyzes an intermediate step in the synthesis of major sterols. The particular biosynthetic pathway varies across eukaryotes. In animals C5SD catalyzes the dehydration of lathosterol to 7-dehydrocholesterol, a step in the synthesis of cholesterol. Cholesterol serves multiple roles in the cell including modulating membrane fluidity serving as a precursor to steroid hormones.
|
|
The protein encoded by this gene is highly similar to the protein product encoded by gene INSIG1. Both INSIG1 protein and this protein are endoplasmic reticulum proteins that block the processing of sterol regulatory element binding proteins (SREBPs) by binding to SREBP cleavage- activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi.
|
|
In 2013, the sterol was reported in the South China Sea gorgonian coral Muriceoopsis flavida. A 9-hydroxylated analogue of cerevisterol was found in R. botrytis. A modified version of the compound, (22E, 24R)-cerevisterol, has been reported from the coral Subergorgia mollis. It was shown to be moderately cytotoxic to embryos of the zebrafish Danio rerio.
|
|
Functions of the cumulus oophorus include coordination of follicular development and oocyte maturation. Mechanisms of the latter include stimulation of amino acid transport and sterol biosynthesis and regulation of oocyte gene transcription. It also provides energy substrates for oocyte meiotic resumption and promotes glycolysis. Cumulus oophorus cells contribute heavily to the maturation and eventual fertilization of an oocyte.
|
|
Cyproconazole inhibits demethylation, a particular step in the synthesis of a component of the fungal cell wall called sterol. This means it affects fungal growth, but not the fungal sporulation. This explains why it must be used when fungal growth is maximum, early in the infection, because in late infections fungal growth slows down and the agent is ineffective.
|
|
The sole proteins containing this domain identified in human are GRAMD1A/Aster-A, GRAMD1B/Aster-B and GRAMD1C/Aster-C (with the VASt domain referred to as an Aster domain). These sterol transfer proteins together with GRAMD2A and GRAMD2B are LAM family proteins, although the latter two lack the VASt domain. Like LAM proteins, GRAMD1 proteins preferentially transfer sterols.
|
|
However, there can be times of sterol starvation. Tetrahymanol biosynthesis does not require oxygen, and can substitute readily for sterols. It is hypothesized that ciliates synthesize tetrahymanol in response to lack of oxygen and exogenous sterols. The gene for tetrahymanol synthase was found in the genomes of many genera of alpha-, delta-, and gammaproteobacteria, including Rhodopseudomonas, Bradyrhizobium and Methylomicrobium.
|
|
LXRβ knockout mice are unaffected by a high-cholesterol diet, suggesting that LXRα and LXRβ have separate roles. LXRs regulate fatty acid synthesis by modulating the expression of sterol regulatory element binding protein-1c (SREBP-1c). LXRs also regulate lipid homeostasis in the brain. LXRα and LXRβ double knockout mice develop neurodegenerative changes in brain tissue.
|
|
The major compounds are sterols, sugars, flavonoids and saponins. Novel crystalline compounds such as clerodolone, clerodone, clerodol, and a sterol designated clerosterol have been isolated from the root. Seven sugars namely raffinose, lactose, maltose, sucrose, galactose, glucose and fructose were identified. Fumaric acid, caffeic acid esters, β-sitosterol and β-sitosterol glucoside were isolated from the flowers.
|
|
Other lipopeptides are toll-like receptor agonists. Lipoproteins are self-assembling molecules that are able to form structures. Certain lipopeptides can have strong antifungal and hemolytic activities. It has been demonstrated that their activity is generally linked to interactions with the plasma membrane, and sterol components of the plasma membrane could play a major role in this interaction.
|
|
This gene encodes a ubiquitously expressed transcription factor that controls cholesterol homeostasis by stimulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix leucine zipper (bHLH-Zip) domain. Various single nucleotide polymorphisms (SNPs) of the SREBF2 have been identified and some of them are found to be associated with higher risk of knee osteoarthritis.
|
|
The species is widespread and can be found in Asia, Australasia, Europe, and both North and South America. The fungus has a history of use in the traditional medicines of native North America and China. Fruit bodies have been analyzed chemically to determine their lipid content, and various chemical derivatives of the fungal sterol ergosterol have been identified.
|
|
ERG11 or Sterol 14-demethylase is a fungal cytochrome P450 enzyme originally from Saccharomyces cerevisiae, belongs to family CYP51, with the CYP Symbol CYP51F1. ERG11 catalyzes the C14-demethylation of lanosterol to 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol which is the first step of biosynthesis of the zymosterol, zymosterol will be further converted into Ergosterol.
|
|
Stigmastanol (sitostanol) is a phytosterol found in a variety of plant sources. Similar to sterol esters and stanol esters, stigmastanol inhibits the absorption of cholesterol from the diet. Animal studies suggest that it also inhibits biosynthesis of cholesterol in the liver. Stigmastanol is the product of the reduction of β-sitosterol and the hydrogenation of stigmasterol.
|
|
Stigmasterol - a plant sterol (phytosterol) - is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E number E499, and may be used in food manufacturing to increase the phytosterol content, potentially lowering the levels of LDL cholesterol.
|
|
After his graduation, Bernal began research under William Henry Bragg at the Davy Faraday Laboratory at the Royal Institution in London. In 1924 he determined the structure of graphite (the Bernal stacking describes the registry of two graphite planes) and also did work on the crystal structure of bronze. His strength was in analysis as much as experimental method, and his mathematical and practical treatment of determining crystal structure was widely studied, but he also developed an X-ray spectro- goniometer. In 1927, he was appointed as the first lecturer in Structural Crystallography at Cambridge, becoming the assistant director of the Cavendish Laboratory in 1934. There, he started applying his crystallographic techniques to organic molecules, starting with oestrin and sterol compounds including cholesterol in 1929, forcing a radical change of thinking among sterol chemists.
|
|
It also contains sterol. Cucumber juice is used as an ingredient in cosmetics, soaps, shampoos, and lotions, and in Eau de toilette and perfumes. It was used in Russian traditional medicine to aid in the treatment of respiratory tract inflammation and to reduce lingering cough. In other traditions it was used to soothe heartburn and reduce acid in the stomach.
|
|
Like amphotericin B and natamycin, nystatin is an ionophore. It binds to ergosterol, a major component of the fungal cell membrane. When present in sufficient concentrations, it forms pores in the membrane that lead to K+ leakage, acidification, and death of the fungus. Ergosterol is a sterol unique to fungi, so the drug does not have such catastrophic effects on animals or plants.
|
|
Using Drosophila as a model organism, Eroglu looked at how metabotropic glutamate receptor (mGluRs) affinity is modulated. She found that when mGluRs are associated with cholesterol rich lipid rafts within the membrane, they exist in a high affinity state for glutamate. When mGluRs are not associated with sterol-rich rafts, they exist in a low affinity state for glutamate binding.
|
|
It has been suggested that SMO is regulated by a small molecule, the cellular localization of which is controlled by PTCH. PTCH1 has homology to Niemann- Pick disease, type C1 (NPC1) that is known to transport lipophilic molecules across a membrane. PTCH1 has a sterol sensing domain (SSD), which has been shown to be essential for suppression of SMO activity.
|
|
Momordenol (3β-hydroxy-stigmasta-5,14-dien-16-one) is a natural chemical compound, a sterol found in the fresh fruit of the bitter melon (Momordica charantia). The compound is soluble in ethyl acetate and methanol but not in pure chloroform or petrol. It crystallizes as fine needles that melt at 160-161 °C. It was isolated in 1997 by S. Begum and others.
|
|
In 1988, Brown received the National Medal of Science for his contributions to medicine. In 1993, their trainees Xiaodong Wang and Michael Briggs purified the sterol regulatory element binding proteins (SREBPs). Since 1993, Drs. Brown, Goldstein, and their colleagues have described the unexpectedly complex machinery by which cells maintain the necessary levels of fats and cholesterol in the face of varying environmental circumstances.
|
|
Houwen et al. used IBD sharing to identify the chromosomal location of a gene responsible for benign recurrent intrahepatic cholestasis in an isolated fishing population. Kenny et al. also used an isolated population to fine-map a signal found by a genome-wide association study (GWAS) of plasma plant sterol (PPS) levels, a surrogate measure of cholesterol absorption from the intestine.
|
|
The binding and pore formation of CDC will occur when the concentration of cholesterol exceeds the association capacity of the phospholipids, allowing the excess cholesterol to associate with the toxin. The presence of cholesterol aggregates in an aqueous solution were sufficient to initiate a conformation change and oligomerization of perfringolysin O (PFO), while no changes were seen by perfingolysin O with epicholesterol aggregates in solution. Epicholesterol is a sterol that differs from cholesterol by the orientation of the 3-β-OH group, which is axial in epicholesterol and equatorial in cholesterol. Since the orientation of the hydroxyl group has such an effect on the bind/pore-formation of CDC, the equatorial conformation may be required for docking of the sterol to the binding pocket in domain 4, or to be properly exposed at the surface of lipid structures.
|
|
SREB proteins are indirectly required for cholesterol biosynthesis and for uptake and fatty acid biosynthesis. These proteins work with asymmetric sterol regulatory element (StRE). SREBPs have a structure similar to E-box-binding helix-loop-helix (HLH) proteins. However, in contrast to E-box-binding HLH proteins, an arginine residue is replaced with tyrosine making them capable of recognizing StREs and thereby regulating membrane biosynthesis.
|
|
Most patients with SLOS present decreased cholesterol levels, particularly in the brain (where cholesterol levels rely primarily on new synthesis). This also means that any sterol derivatives of cholesterol would also have reduced concentrations. For example, reduced levels of neurosteroids may be seen in SLOS. These are lipids which take part in signaling within the brain, and must be produced within the brain itself.
|
|
Scientists have found that tomato plants engineered with the C-5 sterol desaturase from the mushroom Flammulina velutipes show improved drought tolerance and fungal pathogen resistance as well as increased iron and polyunsaturated fat content. The authors of the study suggest that the fungal enzyme may be a useful tool for plant biotechnology as improving multiple aspects of a crop is typically time- and labor-intensive.
|
|
Aramchol activates cholesterol efflux by stimulating (2 to 4-fold) the ABCA1 transporter, a universal cholesterol export pump present in all cells. In animal models, this led to a significant reduction of blood and body cholesterol and an increase in fecal sterol output, mostly neutral sterols. Aramchol is the first small molecule that was shown to induce ABCA1-dependent cholesterol efflux without affecting transcriptional control.
|
|
OSBP plays also a role as a sterol-regulated scaffolding protein for several cytosolic reactions including the phosphorylation of ERK 1/2. It has been shown that expression and maturation of SREBP-1c is controlled by OSBP. SREBP-1c is a major transcription factor for hepatic lipogenesis (fatty acids and triglycerides biosynthesis). OSBP expression levels in transgenic mice affect liver and serum TG levels.
|
|
G. obscuriglobus is one of the few prokaryotes known to synthesize sterols, a process critical to the maintenance of eukaryotic cell membranes and ubiquitous in eukaryotes. The sterols identified in the bacterium, lanosterol and parkeol, are relatively simple compared to eukaryotic sterols; as indicated by phylogenetic analysis, the G. obscuriglobus sterol biosynthetic pathway was among the most primitive known at the time it was identified.
|
|
Oxysterol-binding protein-related protein 5 is a protein that in humans is encoded by the OSBPL5 gene. This gene encodes a member of the oxysterol- binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Transcript variants encoding different isoforms have been identified.
|
|
AEBSF is extensively used in studies aiming to describe cholesterol regulatory genes due to its potent ability to inhibit Site-1-protease (S1P). This serine protease, located in the Golgi apparatus, is responsible for activating the sterol regulatory element-binding proteins (SREBP). By selectively inhibiting S1P, AEBSF can be used to characterize the downstream result of SREBP inhibition and its influence on cholesterol regulation.
|
|
Cholesterol is a sterol, a steroid-like lipid made by animals, including humans. The human body makes one-eighth to one-fourth teaspoons of pure cholesterol daily. A cholesterol level of 5.5 millimoles per litre or below is recommended for an adult. The rise of cholesterol in the body can give a condition in which excessive cholesterol is deposited in artery walls called atherosclerosis.
|
|
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.
|
|
24-Dehydrocholesterol reductase is a protein that in humans is encoded by the DHCR24 gene. This gene encodes a flavin adenine dinucleotide (FAD)-dependent oxidoreductase, which catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. The protein contains a leader sequence that directs it to the endoplasmic reticulum membrane. Missense mutations in this gene have been associated with desmosterolosis.
|
|
FGF21 has been shown to repress the transcription of sterol regulatory element binding protein 1c (SREBP-1c). Overexpression of FGF21 ameliorated the up-regulation of SREBP-1c and fatty acid synthase (FAS) in HepG2 cells elicited by FFAs treatment. Moreover, FGF21 could inhibit the transcriptional levels of the key genes involved in processing and nuclear translocation of SREBP-1c, and decrease the protein amount of mature SREBP-1c.
|
|
Agaric acid is used as an inhibitor of metabolism in several animal experiments. It is shown that this acid prevents the formation of C2 units from citrate and reduces the availability of citrate for the activation of acetyl-CoA carboxylase. Moreover, it has an important role in the metabolism of lipids, because it influences sterol synthesis. Agaric acid induces the mitochondrial permeability transition by collaborating with adenine nucleotide translocase.
|
|
Other mutations are less common, although appear to target certain protein domains more so than others. For example, the sterol reductase motifs are common sites of mutation. Overall, there is an estimated carrier frequency (for any DHCR7 mutation causing SLOS) of 3-4% in Caucasian populations (it is less frequent among Asian and African populations). This number indicates a hypothetical birth incidence between 1/2500 and 1/4500.
|
|
Other hedghehog proteins may be involved in the development of the genital tract and the skeleon. The altered sterol levels in SLOS are particularly relevant to cell membranes, which are made primarily of lipids. SLOS patients may show cell membranes with abnormal properties or composition, and reduced cholesterol levels greatly affect the stability and proteins of lipid rafts. Despite their structural similarity, 7DHC is unable so replace cholesterol in lipid rafts.
|
|
Since enzyme substrate Farnesyl diphosphate has many uses in addition to forming amorpha-4,11-diene, these other pathways regulate ADS. One such pathway is sterol biosynthesis, and in fact, the enzyme squalene synthase (SS) is considered a regulatory switch for ADS. When SS cDNA, which reduces SS mRNA concentration and therefore reduces expression of SS, is introduced into the plant cells, mRNA levels of ADS dramatically increased (Figure 1).
|
|
In at least one patient, a deficiency in C-5 sterol desaturase activity (termed lathosterolosis) was associated with multiple malformations, metal retardation, and liver disease. This patient was also found to have low levels of blood cholesterol and high levels of lathosterol in cell membranes when compared to those of healthy control subjects. These symptoms resemble those of other defects in cholesterol synthesis such as Smith–Lemli–Opitz syndrome.
|
|
Sterol-C4-methyl oxidase-like protein was isolated based on its similarity to the yeast ERG25 protein. It contains a set of putative metal binding motifs with similarity to that seen in a family of membrane desaturases-hydroxylases. The protein is localized to the endoplasmic reticulum membrane and is believed to function in cholesterol biosynthesis. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
|
|
In vitro studies have shown that betulin was effective against a variety of tumors. Betulin causes some types of tumor cells to start a process of self-destruction called apoptosis, and can slow the growth of several types of tumor cells. Another study has shown that betulin inhibited the maturation of sterol regulatory element- binding protein (SREBPs). Inhibition of SREBP by betulin decreased the biosynthesis of cholesterol and fatty acids.
|
|
Heme A has an isoprenoid tail, and lanosterol, the sterol precursor in animals, is derived from squalene and hence from isoprene. The functional isoprene units in biological systems are dimethylallyl pyrophosphate (DMAPP) and its isomer isopentenyl pyrophosphate (IPP), which are used in the biosynthesis of naturally occurring isoprenoids such as carotenoids, quinones, lanosterol derivatives (e.g. steroids) and the prenyl chains of certain compounds (e.g. phytol chain of chlorophyll).
|
|
It is thought that the biosynthesis of calotropin is similar to that of digitoxin, another cardenolide. Digitoxin is more established as a medicine for cardiac insufficiency, and therefore the biosynthesis has been further studied. However, it is believed that many cardenolides are synthesized in plants by a similar process, but this process is not yet well understood. The sterol precursor for this process is similar to precursors for steroidal alkaloids.
|
|
Acyl-CoA cholesterol acyl transferase , more simply referred to as ACAT, also known as sterol O-acyltransferase (SOAT), belongs to the class of enzymes known as acyltransferases. The role of this enzyme is to transfer fatty acyl groups from one molecule to another. ACAT is an important enzyme in bile acid biosynthesis. In nearly all mammalian cells, ACAT catalyzes the intracellular esterification of cholesterol and formation of cholesteryl esters.
|
|
Cultures were diluted in broth medium then passed through membrane filters of various pore diameters, yielding similar results for all nine isolates. Diluted isolates were then tested for reversion, a method of genetic stabilization unique to some bacteria, in both broth and agar medium. No reversion was observed. Isolates were grown in broth medium with large (20%) and minute (0.2%) amounts of fetal bovine serum as a sterol source.
|
|
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. This enzyme is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. This enzyme is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates.
|
|
Human SREBP regulates sterol responsive gene expression, and this regulatory action is conserved in the genetic model organism C. elegans, a roundworm (homologues MDT-15 and SBP-1). Also in C. elegans, MDT-15 is essential for the response to several stresses (fasting, heavy metal, toxin, and oxidative stress); at least in part the fasting response is conferred by interactions of MDT-15 with nuclear receptors, including NHR-49.
|
|
The mammalian σ1 receptor is an integral membrane protein with 223 amino acids. It shows no homology to other mammalian proteins but strikingly shares 30% sequence identity and 69% similarity with the ERG2 gene product of yeast, which is a C 8-C7 sterol isomerase in the ergosterol biosynthetic pathway. Hydropathy analysis of the σ1 receptor indicates three hydrophobic regions. A crystal structure of the σ1 receptor was published in 2016.
|
|
This gene encodes an intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response.[provided by RefSeq, Aug 2009].
|
|
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.
|
|
In enzymology, a sterol-4alpha-carboxylate 3-dehydrogenase (decarboxylating) () is an enzyme that catalyzes the chemical reaction :3beta-hydroxy-4beta- methyl-5alpha-cholest-7-ene-4alpha-carboxylate + NAD(P)+ \rightleftharpoons 4alpha-methyl-5alpha-cholest-7-en-3-one + CO2 \+ NAD(P)H The 3 substrates of this enzyme are 3beta-hydroxy-4beta-methyl-5alpha-cholest-7-ene-4alpha- carboxylate, NAD+, and NADP+, whereas its 4 products are 4alpha-methyl-5alpha- cholest-7-en-3-one, CO2, NADH, and NADPH. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 3beta- hydroxy-4beta-methyl-5alpha-cholest-7-ene-4alpha-carboxylate:NAD(P)+ 3-oxidoreductase (decarboxylating). Other names in common use include 3beta- hydroxy-4beta-methylcholestenecarboxylate 3-dehydrogenase, (decarboxylating), 3beta-hydroxy-4beta-methylcholestenoate dehydrogenase, 3beta-hydroxy-4beta- methylcholestenoate dehydrogenase, and sterol 4alpha-carboxylic decarboxylase.
|
|
The mature form then migrates to the nucleus, where it activates the promoter of genes involved in cholesterol uptake or in cholesterol synthesis. SREBP processing can be controlled by the cellular sterol content. Animal cells maintain proper levels of intracellular lipids (fats and oils) under widely varying circumstances (lipid homeostasis). For example, when cellular cholesterol levels fall below the level needed, the cell makes more of the enzymes necessary to make cholesterol.
|
|
The protein is most prevalent in the kidney and the liver where it is found in Kupffer cells. STARD5 binds both cholesterol and 25-hydroxycholesterol and appears to function to redistribute cholesterol to the endoplasmic reticulum with which the protein associates and/or the plasma membrane. Increased levels of StarD5 increase free cholesterol in the cell. Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g.
|
|
Phytosterols, which encompass plant sterols and stanols, are phytosteroids, similar to cholesterol, which occur in plants and vary only in carbon side chains and/or presence or absence of a double bond. Stanols are saturated sterols, having no double bonds in the sterol ring structure. More than 200 sterols and related compounds have been identified. Free phytosterols extracted from oils are insoluble in water, relatively insoluble in oil, and soluble in alcohols.
|
|
Oxysterol-binding protein-related protein 8 is a protein that in humans is encoded by the OSBPL8 gene. This gene encodes a member of the oxysterol- binding protein (OSBP) family, a group of intravenous lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Two transcript variants encoding different isoforms have been found for this gene.
|
|
In the first taxonomy of Mollicutes, the classification was based on requiring or not requiring cholesterol for growth. The old order Mycoplasmatales consisted of two families: Mycoplasmataceae, which requires cholesterol, and the sterol-nonrequiring Acholeplasmataceae. In view of the many properties in which the acholeplasmas distinguish from species in Mycoplasmataceae and Spiroplasmataceae, Freundt et al. proposed in 1984 to elevate the family Acholeplasmataceae to the ordinal rank Acholeplasmatales, thus separating it from Mycoplasmatales.
|
|
Lactarius sanguifluus contains a mixture of sterols. The predominant sterol is ergosterol (56.6% of total sterols), with lesser amounts of ergosterol derivatives, including ergost-7-en-3β-ol, ergosta-7,22-dien-3β-ol, and ergosta-5,7-dien-3β-ol. The latex contains sesquiterpene pigments with guaiane skeletons; these include the compounds given the common names lactaroviolin and sangol. Some of these chemicals are thought to undergo enzymatic conversions when the fruit body becomes injured.
|
|
Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (sterol regulatory element-binding protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL-receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.
|
|
Based on microbial physiology studies, gammacerane was suggested as a potential biomarker for ocean stratification. When water columns stratify, anoxic conditions can form in the bottom waters. Ciliates living in these conditions must adapt to produce lipids that do not require molecular oxygen for their biosynthesis. A direct correlation between sterol availability and tetrahymanol synthesis in ciliates has been shown, leading to the hypothesis that gammacerane in sediments is a biomarker for ocean stratification.
|
|
Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, the enzymes that synthesize it have become important targets for drug discovery. In human nutrition, ergosterol is a provitamin form of vitamin D2; exposure to ultraviolet (UV) light causes a chemical reaction that produces vitamin D2.
|
|
Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family. SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell. SREBP-1a and SREBP-1c are both encoded by the same gene, but are transcribed by different promoters.
|
|
The sigma receptors σ1 and σ2 bind to ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. They are named by pharmacological similarities, and are evolutionarily unrelated. The fungal protein ERG2, a C-8 sterol isomerase, falls into the same protein family as sigma-1. Both localize to the ER membrane, although sigma-1 is also reported to be a cell surface receptor.
|
|
The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atherosclerosis, and have been observed in patients with sitosterolemia.
|
|
In plants, mevalonate is the precursor of all isoprenoid compounds. The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG- CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids. Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region.
|
|
Not only do transcription factors act downstream of signaling cascades related to biological stimuli but they can also be downstream of signaling cascades involved in environmental stimuli. Examples include heat shock factor (HSF), which upregulates genes necessary for survival at higher temperatures, hypoxia inducible factor (HIF), which upregulates genes necessary for cell survival in low-oxygen environments, and sterol regulatory element binding protein (SREBP), which helps maintain proper lipid levels in the cell.
|
|
Two molecules of FPP are then joined tail-to-tail to yield squalene, a triterpene. Squalene, through a cyclization reaction with 2,3-oxidosqualene 6 as an intermediate forms cycloartenol. The double bond of cycloartenol (compound 7 in diagram) is methylated by SAM to give a carbocation that undergoes a hydride shift and loses a proton to yield a compound with a methylene side-chain. Both of these steps are catalyzed by sterol C-24 methyltransferase (Step E1 in diagram).
|
|
Slotta, a sterol chemist, studied medical applications of snake venom. In 1938, Slotta and his brother-in-law Heinz Fraenkel-Conrat isolated crotoxin from venom, the first snake toxin to be isolated in crystalline form. Their research suggested that the toxicity of crotoxin was due to effects on nerve lipids. He subsequently co-founded a biopharmaceutical company.Hawgood, Babara J.,Karl Heinrich Slotta (1895–1987) Biochemist: Snakes, Pregnancy and Coffee, Toxicon, Volume 39, Issue 9, September 2001, Pages 1277–1282.
|
|
Squalene monooxygenase (also called squalene epoxidase) is an enzyme that uses NADPH and molecular oxygen to oxidize squalene to 2,3-oxidosqualene (squalene epoxide). Squalene epoxidase catalyzes the first oxygenation step in sterol biosynthesis and is thought to be one of the rate-limiting enzymes in this pathway. In humans, squalene epoxidase is encoded by the SQLE gene. Several eukaryote genomes lack a squalene monooxygenase encoding gene, but instead encode an alternative squalene epoxidase that catalyzes the oxidation of squalene.
|
|
Butyrophilin is the major protein associated with fat droplets in the milk. This gene is a member of the BTN2 subfamily of genes, which encode proteins belonging to the butyrophilin protein family. The gene is located in a cluster on chromosome 6, consisting of seven genes belonging to the expanding B7/butyrophilin-like group, a subset of the immunoglobulin gene superfamily. The encoded protein is a type 1 receptor glycoprotein involved in lipid, fatty-acid and sterol metabolism.
|
|
CYP7A1 is upregulated by the nuclear receptor LXR (liver X receptor) when cholesterol (to be specific, oxysterol) levels are high. The effect of this upregulation is to increase the production of bile acids and reduce the level of cholesterol in hepatocytes. It is downregulated by Sterol regulatory element- binding proteins (SREBP) when plasma cholesterol levels are low. Bile acids provide feedback inhibition of CYP7A1 by at least two different pathways, both involving the farnesoid X receptor, FXR.
|
|
Cholesterol is converted mainly into coprostanol, a nonabsorbable sterol that is excreted in the feces. Although cholesterol is a steroid generally associated with mammals, the human pathogen Mycobacterium tuberculosis is able to completely degrade this molecule and contains a large number of genes that are regulated by its presence. Many of these cholesterol-regulated genes are homologues of fatty acid β-oxidation genes, but have evolved in such a way as to bind large steroid substrates like cholesterol.
|
|
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.
|
|
Liu graduated first in his class at Harvard in 1994. He performed organic and bioorganic chemistry research on sterol biosynthesis under Professor E. J. Corey's guidance as an undergraduate. During his Ph.D. research with Professor Peter Schultz at U. C. Berkeley, Liu initiated the first general effort to expand the genetic code in living cells. He earned his Ph.D. in 1999 and became assistant professor of chemistry and chemical biology at Harvard University in the same year.
|
|
Recent findings suggest that StAR may also traffic cholesterol to a second mitochondrial enzyme, sterol 27-hydroxylase. This enzyme converts cholesterol to 27-hydroxycholesterol. In this way it may be important for the first step in one of the two pathways for the production of bile acids by the liver (the alternative pathway). Evidence also shows that the presence of StAR in a type of immune cell, the macrophage, where it can stimulate the production of 27-hydroxycholesterol.
|
|
The most prevalent dietary minerals in sea buckthorn fruits are potassium (300–380 mg/100 g), manganese (0.28–0.32 mg/100 g), and copper (0.1 mg/100 g). The fruit is also rich in phytosterols (340–520 mg/kg), β-sitosterol being the major sterol compound as it constitutes 57–83% of total sterols. Flavonols were found to be the predominating class of phenolic compounds, while phenolic acids and flavan-3-ols (catechins) represent minor components.
|
|
In addition to the physodic acid mentioned above, P. furfuracea also contains 2-hydroxy-4-methoxy-3,6-dimethyl benzoic acid, atranorin, oxyphysodic acid, and virensic acid. Of these compounds, atranorin showed the highest inhibition of proteolytic enzymes trypsin and porcine pancreatic elastase. Research suggests that the biosynthesis of both atranorin and physodic acid is influenced by the cooperation of epiphytic bacteria. A number of sterol compounds have been identified from P. furfuracea, including ergosterol peroxide, ergosterol and lichosterol.
|
|
HMG CoA reductase occurs early in the biosynthetic pathway and is among the first committed steps to cholesterol formulation. Inhibition of this enzyme could lead to accumulation of HMG CoA, a water-soluble intermediate that is, then, capable of being readily metabolized to simpler molecules. This inhibition of reductase would lead to accumulation of lipophylic intermediates with a formal sterol ring. Lovastatin was the first specific inhibitor of HMG CoA reductase to receive approval for the treatment of hypercholesterolemia.
|
|
Capacitation is the penultimate step in the maturation of mammalian spermatozoa and is required to render them competent to fertilize an oocyte. This step is a biochemical event; the sperm move normally and look mature prior to capacitation. In vivo, capacitation occurs after ejaculation, when the spermatozoa leave the vagina and enter the superior female reproductive tract. The uterus aids in the steps of capacitation by secreting sterol- binding albumin, lipoproteins, and proteolytic and glycosidasic enzymes such as heparin.
|
|
High blood cholesterol, also called hypercholesterolemia, significantly increases the risk of stroke, heart attack, and peripheral artery disease. If untreated, it can also lead to plaque accumulation in blood vessels, which is known as atherosclerosis. For this reason, the sterol biosynthetic pathway has long been a target for the drug development industry. Statins, which inhibit HMG-CoA reductase (an enzyme that catalyzes an earlier step in the cholesterol biosynthesis pathway) are commonly prescribed to treat high cholesterol.
|
|
Growth was inhibited in the latter, indicating dependence on an outside sterol source for growth. The 16S rRNA gene was sequenced, yielding a unique sequence, suggesting the discovery of a previously unidentified organism. The Brown study in 2001 further investigated the pathogenicity of the newly discovered M. alligatoris by inoculation of four healthy alligators with the bacteria and one control alligator inoculated with sterile broth. Three of the experimental alligators died within three weeks of inoculation.
|
|
The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)". They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. The structure was worked out by Schering's Adolf Butenandt, at the Chemisches Institut of Technical University in Gdańsk. The chemical synthesis of testosterone from cholesterol was achieved in August that year by Butenandt and Hanisch.
|
|
In enzymology, a cholestanetriol 26-monooxygenase () is an enzyme that catalyzes the chemical reaction :5beta-cholestane-3alpha,7alpha,12alpha-triol + NADPH + H+ \+ O2 \rightleftharpoons (25R)-5beta- cholestane-3alpha,7alpha,12alpha,26-tetraol + NADP+ \+ H2O The 4 substrates of this enzyme are 5beta-cholestane-3alpha,7alpha,12alpha-triol, NADPH, H+, and O2, whereas its 3 products are (25R)-5beta- cholestane-3alpha,7alpha,12alpha,26-tetraol, NADP+, and H2O. This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as one donor, and incorporation of one atom o oxygen into the other donor. The systematic name of this enzyme class is 5beta- cholestane-3alpha,7alpha,12alpha-triol,NADPH:oxygen oxidoreductase (26-hydroxylating). Other names in common use include 5beta- cholestane-3alpha,7alpha,12alpha-triol 26-hydroxylase, 5beta- cholestane-3alpha,7alpha,12alpha-triol hydroxylase, cholestanetriol 26-hydroxylase, sterol 27-hydroxylase, sterol 26-hydroxylase, cholesterol 27-hydroxylase, CYP27A, CYP27A1, and cytochrome P450 27A1'.
|
|
INSIG always stays in the ER membrane and thus the SREBP-SCAP complex remains in the ER when SCAP is bound to INSIG. When sterol levels are low, INSIG and SCAP no longer bind. Then, SCAP undergoes a conformational change that exposes a portion of the protein ('MELADL') that signals it to be included as cargo in the COPII vesicles that move from the ER to the Golgi apparatus. In these vesicles, SCAP, dragging SREBP along with it, is transported to the Golgi.
|
|
Azacosterol (), or azacosterol hydrochloride () (brand name Ornitrol), also known as 20,25-diazacholesterol, is a cholesterol-lowering drug (hypocholesteremic) which was marketed previously but has since been discontinued. It is also an avian chemosterilant used to control the pest pigeon population via inducing sterility. The drug is a sterol and derivative of cholesterol in which two carbon atoms have been replaced with nitrogen atoms. Azacosterol acts as an inhibitor of 24-dehydrocholesterol reductase (24-DHCR), preventing the formation of cholesterol from desmosterol.
|
|
OSBP is regulated by PKD mediated phosphorylation, and by the oxysterol 25-hydroxycholesterol (25-OH), a high-affinity ligand for OSBP (~30 nM). Several proteins involved in cholesterol homeostasis, such as INSIG-1 or ACAT, also bind 25-OH. In fact 25-OH is a potent suppressor of sterol synthesis in cultured cells and accelerates cholesterol esterification. In cellular studies it has been shown that OSBP, initially cytosolic, relocates to ER-Golgi membrane contact sites in the presence of 25-OH.
|
|
Membrane-bound transcription factor site-2 protease, or site-2 protease (S2P) for short, is an enzyme () encoded by the gene which liberates the N-terminal fragment of sterol regulatory element-binding protein (SREBP) transcription factors from membranes. S2P cleaves the transmembrane domain of SREPB, making it a member of the class of intramembrane proteases. S2P endopeptidase () is an enzyme. This enzyme catalyses the following chemical reaction : Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains.
|
|
Myosin regulatory light chain interacting protein, also known as MYLIP, is a protein that in humans is encoded by the MYLIP gene. MYLIP is also known as IDOL "Inducible Degrader of the LDL receptor" based on its involvement in cholesterol regulation. The expression of IDOL is induced by the sterol- activated liver X receptor. Increased Degradation of LDL Receptor Protein (IDOL) is a ubiquitin ligase that ubiquinates LDL receptors in endosomes and directs the receptors to the lysosomal compartment for degradation.
|
|
Research into the natural product chemistry of Coprinellus micaceus has revealed the presence of several chemical compounds unique to the species. Micaceol is a sterol with "modest" antibacterial activity against the pathogens Corynebacterium xerosis and Staphylococcus aureus. The compound (Z,Z)-4-oxo-2,5-heptadienedioic acid has inhibitory activity against glutathione S-transferase, an enzyme that has been implicated in the resistance of cancer cells against chemotherapeutic agents, especially alkylating drugs. A 2003 study did not find any antibacterial activity in this species.
|
|
Another measure of human faecal contamination is the proportion of the two 3β-ol isomers of the saturated sterol form. 5α-cholestanol is formed naturally in the environment by bacteria and generally does not have a faecal origin. Samples with ratios greater than 0.7 may be contaminated with human faecal matter; samples with values less than 0.3 may be considered uncontaminated. Samples with ratios between these two cut-offs can not readily be categorised on the basis of this ratio alone.
|
|
Two suggested pathways, the pregnane pathway and norcholanic acid pathway are possible for the conversion of the sterol precursor to digitoxigenin, the precursor to digitoxin. Both the pregnane and norcholanic acid pathways use progesterone 5β-reductases, the P5βR and P5βR2 respectively. In the pregnane pathway, a plant analog of the mitochondrial cytochrome P450 (CYP11A in humans), is thought to catalyze the conversion of pregnenolone to progesterone. Progesterone is further processed by P5βR to 5β-Pregnane-3,20-dione, and then to digitoxigenin.
|
|
Phytochemical analysis of Silene jenisseensis roots have found ecdysteroid 20-hydroxyecdysone, sterol α-spinasterol-3-O-glucoside, triterpenoids quillaic acid derivatives — jenisseensoside A, B, C and D. In herb of Silene jenisseensis flavone-C-glycosides were detected including vitexin, isovitexin, orientin, isoorientin, as well as ecdysteroids 2-desoxyecdysone, 2-desoxy-20-hydroxyecdysone, ponasterone A, dacryhainansterone, 20-hydroxyecdysone and integristerone A. Total content of ecdysteroids in Silene jenisseensis roots and herb collected in Buryatia Republic was 0.06% and 0.06—0.83%, respectively.
|
|
Like most leucoplasts, elaioplasts are non-pigmented organelles capable of alternating between the different forms of plastids. The elaioplast specifically is primarily responsible for the storage and metabolism of lipids, among these roles, recent studies have shown that these organelles participate in the formation of terpenes and fatty acids. Typically, they appear as small, rounded organelles filled by oil droplets. Lipids found inside elaioplasts mirror those synthesized by prokaryotes, chiefly triacylglycerol and sterol esters, which cluster into the droplets visible by microscope.
|
|
The structural and functional properties of the cytochrome P450 superfamily have been subject to extensive diversification over the course of evolution. Recent estimates indicate that there are currently 10 classes and 267 families of CYP proteins. It is believed that 14α-demethylase or CYP51 diverged early in the cytochrome's evolutionary history and has preserved its function ever since; namely, the removal of the 14α-methyl group from sterol substrates. Although CYP51's mode of action has been well conserved, the protein's sequence varies considerably between biological kingdoms.
|
|
Evidence shows that the doses that provide the most control of the disease also provide the largest selection pressure to acquire resistance, and that lower doses decrease the selection pressure.Metcalfe, R.J. et al. (2000) The effect of dose and mobility on the strength of selection for DMI (sterol demethylation inhibitors) fungicide resistance in inoculated field experiments. Plant Pathology 49: 546–557 In some cases when a pathogen evolves resistance to one fungicide, it automatically obtains resistance to others – a phenomenon known as cross resistance.
|
|
This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. It is also essential for the production of Crotonyl-CoA which activates its target genes by crotonylation of histone tails. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids.
|
|
A current theory suggests that PTCH regulates SMO by removing oxysterols from SMO. PTCH acts like a sterol pump and removes oxysterols that have been created by 7-dehydrocholesterol reductase. Upon binding of a Hh protein or a mutation in the SSD of PTCH, the pump is turned off allowing oxysterols to accumulate around SMO. Suggested regulation pathway for Smo via Hedgehog and Ptch1 This accumulation of sterols allows SMO to become active or stay on the membrane for a longer period of time.
|
|
Some representative hopanoids: A. Diploptene, also called 22(29)-hopene B. Diplopterol, also called hopan-22-ol, the hydrated cyclomer of diploptene C. Bacteriohopanetetrol (BHT), a common extended hopanoid D. Hopane, the diagenetic product of A and B that results from reducing conditions during deposition and persists in the rock record. The diagenetic product of C would be an extended C35 hopane. Cholesterol, a sterol compound found in all eukaryotes. Hopanoids are a diverse subclass of triterpenoids with the same hydrocarbon skeleton as the compound hopane.
|
|
About 10% of sequenced bacterial genomes have a putative shc gene encoding a squalene-hopene cyclase and can presumably make hopanoids, which have been shown to play diverse roles in the plasma membrane and may allow some organisms to adapt in extreme environments. Since hopanoids modify plasma membrane properties in bacteria, they are frequently compared to sterols (e.g., cholesterol), which modulate membrane fluidity and serve other functions in eukaryotes. Although hopanoids do not rescue sterol deficiency, they are thought to increase membrane rigidity and decrease permeability.
|
|
Posaconazole works by disrupting the close packing of acyl chains of phospholipids, impairing the functions of certain membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system, thus inhibiting growth of the fungi. It does this by blocking the synthesis of ergosterol by inhibiting of the enzyme lanosterol 14α-demethylase and accumulation of methylated sterol precursors. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than itraconazole.Brunton L, Lazo J, Parker K. Goodman and Gilman's The Pharmacological Basis of Therapeutics.
|
|
Sterol is a chemical compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. The name is also used generically for compounds that are derived from this one by substituting other chemical groups for some of the hydrogen atoms, or modifying the bonds in the ring. These sterols or steroid alcohols are a subgroup of the steroids and an important class of organic molecules.
|
|
There are currently no successful methods in controlling the severity and occurrence of the disease on a commercial scale ,. No fungicides and soil fumigation strategies have proved successful. Chemicals such as methyl bromide, anhydrous ammonia and ammonium salts were tested as effective but required deep injective into the soil, therefore expensive and not commercially feasible. In addition, systemic fungicides such as benzimidazoles and sterol biosynthesis inhibitors were shown to limit P. omnivore as well, but systemic fungicides are expensive, and exhibit poor soil penetration therefore pursued cautiously.
|
|
Momordicin-28 or 13-hydroxy-28-methoxy-urs-11-en-3-one is a triterpene compound with formula found in the fresh fruit of the bitter melon (Momordica charantia).Sabira Begum, Mansour Ahmed, Bina S. Siddiqui, Abdullah Khan, Zafar S. Saify, and Mohammed Arif (1997), Triterpenes, a sterol and a monocyclic alcohol from Momordica charantia. Phytochemistry, volume 44, issue 7, pages 1313-1320 The compound is soluble in ethyl acetate and chloroform but not in petrol. It crystallizes as fine needles that melt at 121−122 °C.
|
|
In enzymology, a triacylglycerol---sterol O-acyltransferase () is an enzyme that catalyzes the chemical reaction :triacylglycerol + a 3beta-hydroxysterol \rightleftharpoons diacylglycerol + a 3beta-hydroxysterol ester Thus, the two substrates of this enzyme are triacylglycerol and 3beta-hydroxysterol, whereas its two products are diacylglycerol and 3beta-hydroxysterol 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 triacylglycerol:3beta-hydroxysterol O-acyltransferase. This enzyme is also called triacylglycerol:sterol acyltransferase.
|
|
A PCSK9-sortilin interaction is proposed to be required for cellular secretion of PCSK9. In healthy humans, plasma PCSK9 levels directly correlate with plasma sortilin levels, following a diurnal rhythm similar to cholesterol synthesis. The plasma PCSK9 concentration is higher in women compared to men, and the PCSK9 concentrations decrease with age in men but increase in women, suggesting that estrogen level most likely plays a role. PCSK9 gene expression can be regulated by sterol-response element binding proteins (SREBP-1/2), which also controls LDLR expression.
|
|
Most fibrates can cause mild stomach upset and myopathy (muscle pain with CPK elevations). Fibrates decrease the synthesis of bile acid by down-regulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression, therefore making it easier for cholesterol to precipitate and increasing the risk for gallstones. In combination with statin drugs, fibrates cause an increased risk of rhabdomyolysis, idiosyncratic destruction of muscle tissue, leading to kidney failure. The less lipophilic statins are less prone to cause this reaction, and are probably safer when combined with fibrates.
|
|
Subsequently, RIP was found to be used in almost all organisms from bacteria to human beings and regulates a wide range of processes ranging from development to neurodegeneration. A feature of the SREBP pathway is the proteolytic release of a membrane-bound transcription factor, SREBP. Proteolytic cleavage frees it to move through the cytoplasm to the nucleus. Once in the nucleus, SREBP can bind to specific DNA sequences (the sterol regulatory elements or SREs) that are found in the control regions of the genes that encode enzymes needed to make lipids.
|
|
Although the polyene macrolide antibiotics exhibit potent antifungal activity, most are too toxic for therapeutic applications, with the exceptions of amphotericin B and nystatin A1. Unlike amphotericin B and nystatin A1 which form sterol-dependent ion channels, filipin is thought to be a simple membrane disrupter. Since filipin is highly fluorescent and binds specifically to cholesterol, it has found widespread use as a histochemical stain for cholesterol. This method of detecting cholesterol in cell membranes is used clinically in the study and diagnosis of Type C Niemann-Pick disease.
|
|
Squalene synthase (SQS) or farnesyl-diphosphate:farnesyl-diphosphate farnesyl transferase is an enzyme localized to the membrane of the endoplasmic reticulum. SQS participates in the isoprenoid biosynthetic pathway, catalyzing a two-step reaction in which two identical molecules of farnesyl pyrophosphate (FPP) are converted into squalene, with the consumption of NADPH. Catalysis by SQS is the first committed step in sterol synthesis, since the squalene produced is converted exclusively into various sterols, such as cholesterol, via a complex, multi-step pathway. SQS belongs to squalene/phytoene synthase family of proteins.
|
|
Based on its amino acid profile C-5 sterol desaturase appears to have four to five membrane-spanning regions, suggesting that it is a transmembrane protein. C5SD activity has been demonstrated in microsomes from rat tissue, implying that rat enzyme localizes to the endoplasmic reticulum Fluorescence microscopy experiments have shown that in the ciliate Tetrahymena thermophila C5SD localizes to the endoplasmic reticulum and that in S. cerevisiae C5SD localizes to both the endoplasmic reticulum and vesicles. In Arabidopsis thaliana C5SD is located in both the endoplasmic reticulum and lipid particles.
|
|
Many synthetic steroidic compounds like some sexual hormones frequently appear in municipal and industrial wastewaters, acting as environmental pollutants with strong metabolic activities negatively affecting the ecosystems. Since these compounds are common carbon sources for many different microorganisms their aerobic and anaerobic mineralization has been extensively studied. The interest of these studies lies on the biotechnological applications of sterol transforming enzymes for the industrial synthesis of sexual hormones and corticoids. Very recently, the catabolism of cholesterol has acquired a high relevance because it is involved in the infectivity of the pathogen Mycobacterium tuberculosis (Mtb).
|
|
As a result of the discovery, LDL receptor function had also elucidated the principle of receptor-mediated endocytosis—a now universally understood process in cell biology. Goldstein and Brown were awarded the Nobel Prize in Physiology or Medicine for the discovery in 1985. After finishing postdoctoral training, Thomas Südhof started his own laboratory at UT Southwestern in 1986. Briefly continuing work with Goldstein and Brown, Südhof helped identify a DNA element in the LDL gene that produced sterol mediated end-product repression when inserted in a viral promoter.
|
|
Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, whereas lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2). In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP cleavage-activating protein) and INSIG-1.
|
|
When cholesterol levels fall, INSIG-1 dissociates from the SREBP-SCAP complex, which allows the complex to migrate to the Golgi apparatus. Here SREBP is cleaved by S1P and S2P (site-1 protease and site-2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus, and acts as a transcription factor to bind to the sterol regulatory element (SRE), which stimulates the transcription of many genes. Among these are the low-density lipoprotein (LDL) receptor and HMG-CoA reductase.
|
|
Intramuscular triacylglycerol serves as an energy store that can be used during exercise, when it may contribute up to 20% of total energy turnover (depending on diet, gender, and exercise type). Scientists think that a low- calorie diet and exercise-induced proteins (Sterol regulatory element-binding protein) cause the high levels of IMTG in athletes' skeletal muscle. In contrast, the build-up of IMTG in obese individuals correlates to high levels of adipose tissue. Women have a higher IMTG content and studies have revealed that they use more IMTGs during exercise.
|
|
Patched is part of a negative feedback mechanism for hedgehog signaling that helps shape the spatial gradient of signaling activity across tissues. In the absence of hedgehog, low levels of patched are sufficient to suppress activity of the signal transduction pathway. When hedgehog is present, its cholesterol moiety binds to the sterol-sensing domain in patched, which then inhibits the activity of smoothened. Smoothened is a G protein-coupled receptor, most of which is stored in membrane bound vesicles internally within the cell and which increases at the cell surface when hedgehog is present.
|
|
CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) also known as sterol 12-alpha-hydroxylase is a protein which in humans is encoded by the CYP8B1 gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP8B1 is an endoplasmic reticulum membrane protein and catalyzes the conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one.
|
|
Cholesterol interacts preferentially, although not exclusively, with sphingolipids due to their structure and the saturation of the hydrocarbon chains. Although not all of the phospholipids within the raft are fully saturated, the hydrophobic chains of the lipids contained in the rafts are more saturated and tightly packed than the surrounding bilayer. Cholesterol is the dynamic "glue" that holds the raft together. Due to the rigid nature of the sterol group, cholesterol partitions preferentially into the lipid rafts where acyl chains of the lipids tend to be more rigid and in a less fluid state.
|
|
Squalene-hopene cyclase is found in a large number of bacteria but is most readily isolated from the thermophilic bacterium Alicyclobacillus acidocaldarius. It catalyses the conversion of the acyclic molecule of squalene into the pentacyclic triterpenes of hopene and hopanol. Space-filling model of the squalene molecule Squalene-hopene cyclase is thought to be an evolutionary progenitor of many classes of eukaryotic and prokaryotic sterol cyclases. Oxidosqualene cyclases, which are eukaryotic analogs of SHC require oxygen for their reaction demonstrating a much later evolution when the atmosphere began accumulating oxygen.
|
|
Momordicilin or 24-[1′-hydroxy,1′-methyl-2′-pentenyloxyl]-ursan-3-one is a chemical compound, a triterpenoid with formula , found in the fresh fruit of the bitter melon (Momordica charantia).Sabira Begum, Mansour Ahmed, Bina S. Siddiqui, Abdullah Khan, Zafar S. Saify, and Mohammed Arif (1997), Triterpenes, a sterol and a monocyclic alcohol from Momordica charantia. Phytochemistry, volume 44, issue 7, pages 1313-1320 The compound is soluble in ethyl acetate and chloroform but not in petrol. It crystallizes as needles that melt at 170−171 °C.
|
|
A 2014 study on the nutritional composition and phytochemical composition of the rosehip seed, and the fatty acid and sterol compositions of the seed oil showed that rosehip seed and seed oil were good sources of phytonutrients. Consumption of foods rich in phytonutrients is recommended to reduce the risk of chronic diseases. The nutritional composition and the presence of bioactive compounds make the rosehip seed a valuable source of phytonutrients. The rosehip seed was highly rich in carbohydrates and ascorbic acid, and the rosehip-seed oil was highly rich in polyunsaturated fatty acids and phytosterols.
|
|
Wool fat tin (adeps lanae), at the Centre touristique de la Laine et de la Mode in Verviers, Belgium Lanolin (from Latin 'wool', and 'oil'), also called wool yolk, wool wax, or wool grease, is a wax secreted by the sebaceous glands of wool-bearing animals. Lanolin used by humans comes from domestic sheep breeds that are raised specifically for their wool. Historically, many pharmacopoeias have referred to lanolin as wool fat (adeps lanae); however, as lanolin lacks glycerides (glycerol esters), it is not a true fat. Lanolin primarily consists of sterol esters instead.
|
|
This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as one donor, and incorporation of one atom o oxygen into the other donor. The systematic name of this enzyme class is 5beta-cholestane-3alpha,7alpha-diol,NADPH:oxygen oxidoreductase (12alpha- hydroxylating). Other names in common use include 5beta- cholestane-3alpha,7alpha-diol 12alpha-monooxygenase, sterol 12alpha- hydroxylase (ambiguous), CYP8B1, and cytochrome P450 8B1.
|
|
The amphipathic nature of saponins gives them activity as surfactants with potential ability to interact with cell membrane components, such as cholesterol and phospholipids, possibly making saponins useful for development of cosmetics and drugs. Saponins have also been used as adjuvants in development of vaccines, such as Quil A, an extract from the bark of Quillaja saponaria. This makes them of interest for possible use in subunit vaccines and vaccines directed against intracellular pathogens. In their use as adjuvants for manufacturing vaccines, toxicity associated with sterol complexation remains a concern.
|
|
As an antifungal, ketoconazole is structurally similar to imidazole, and interferes with the fungal synthesis of ergosterol, a constituent of fungal cell membranes, as well as certain enzymes. As with all azole antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14α-demethylase (CYP51A1). This enzyme participates in the sterol biosynthesis pathway that leads from lanosterol to ergosterol. Lower doses of fluconazole and itraconazole are required to kill fungi compared to ketoconazole, as they have been found to have a greater affinity for fungal cell membranes.
|
|
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.
|
|
After undergraduate study in London, she undertook a PhD at Swansea University followed by postdoctoral work at the University of Sheffield, researching microbial cytochromes P450. After a position at Aberystwyth University she returned to Swansea University Medical School as Reader and then Professor. She continues to research sterol metabolism and microbial cytochromes P450 as targets for antifungal agents in medicine and agriculture, and has authored over fifty papers on these subjects. She is a member of the BBSRC pool of experts and Natural Products (NPRONET, NIBB) board member.
|
|
The only method for preparing this drug prior to 1952 was a lengthy synthesis starting from cholic acid isolated from bile. In 1952 two Upjohn biochemists, Dury Peterson and Herb Murray announced that they were able to introduce this crucial oxygen atom by fermentation of the steroid progesterone with a common mold of the genus Rhizopus. Over the next several years a group of chemists headed by John Hogg developed a process for preparing cortisone from the soybean sterol stigmasterol. The microbiological oxygenation is a key step in this process.
|
|
Lichtenstein has spent her research career assessing the interplay between diet and heart disease risk factors. In her capacity as director of the Cardiovascular Nutrition Laboratory, Lichtenstein oversees research projects on a wide range of nutrition and cardiovascular disease related topics. Her research interests have included trans fatty acids; soy protein and isoflavones; sterol and stanol esters; modified vegetable oils with different fatty acid profiles, glycemic indexes and biomarkers of nutrient and food intake. Investigations have been conducted in animal models, cell systems, humans, and in population-based studies.
|
|
Participants followed the TLC diet for 5 weeks followed by 6 weeks of either the sterol/stanol capsule or a placebo before crossing over to the other product for 6 weeks while continuing the TLC diet. Results indicated that incorporating sterols/stanols into the TLC diet produced positive changes in LDL cholesterol by 9.2%, total cholesterol by 7.4%, and triglycerides by 9.1%. A following study replicated this original study design, supporting the efficacy of 1.8 grams/day of esterified plant sterols/stanols in adjunct with the TLC diet to reduce lipid levels in participants with hypercholesterolemia.
|
|
SR144528 is a drug that acts as a potent and highly selective CB2 receptor inverse agonist, with a Ki of 0.6 nM at CB2 and 400 nM at the related CB1 receptor. It is used in scientific research for investigating the function of the CB2 receptor, as well as for studying the effects of CB1 receptors in isolation, as few CB1 agonists that do not also show significant activity as CB2 agonists are available. It has also been found to be an inhibitor of sterol O-acyltransferase, an effect that appears to be independent from its action on CB2 receptors.
|
|
In 1929 he was invited by R.B. Bourdillon at NIMR in Hampstead to join him in work on vitamin D. The structure of vitamin D was unknown at that time, and the structure of steroids in general was a matter of debate. A meeting took place with J.B.S. Haldane, J.D. Bernal and Dorothy Crowfoot to discuss possible structures, which contributed to bringing a team together. X-ray crystallography demonstrated that sterol molecules were flat, not as previously proposed by Adolf Windaus. In 1932 Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance.
|
|
Until the discovery of the Poribacteria, planctomycetes were the only bacteria known with these apparent internal compartments. Three-dimensional electron tomography reconstruction of a representative species, Gemmata obscuriglobus, has yielded varying interpretations of this observation. One 2013 study found the appearance of internal compartments to be due to a densely invaginated but continuous single membrane, concluding that only the two compartments typical of Gram-negative bacteria - the cytoplasm and periplasm - are present. However, the excess membrane triples the surface area of the cell relative to its volume, which may be related to Gemmata's sterol biosynthesis abilities.
|
|
Cholesterol needs to be transferred from the outer mitochondrial membrane to the inner membrane where cytochrome P450scc enzyme (CYP11A1) cleaves the cholesterol side chain, which is the first enzymatic step in all steroid synthesis. The aqueous phase between these two membranes cannot be crossed by the lipophilic cholesterol, unless certain proteins assist in this process. A number of proteins have historically been proposed to facilitate this transfer including: sterol carrier protein 2 (SCP2), steroidogenic activator polypeptide (SAP), peripheral benzodiazepine receptor (PBR or translocator protein, TSPO), and StAR. It is now clear that this process is primarily mediated by the action of StAR.
|
|
In 1949, American research chemist Percy Lavon Julian, in looking for ways to produce cortisone, announced the synthesis of the Compound S, from the cheap and readily available pregnenolone (synthesized from the soybean oil sterol stigmasterol). On April 5, 1952, biochemist Durey Peterson and microbiologist Herbert Murray at Upjohn, published the first report of a breakthrough fermentation process for the microbial 11α-oxygenation of steroids (e.g. progesterone) in a single step by common molds of the order Mucorales. 11α-oxygenation of Compound S produces 11α-hydrocortisone, which can be chemically oxidized to cortisone, or converted by further chemical steps to 11β-hydrocortisone (cortisol).
|
|
Pierre Benveniste's work is carried out in the field of biosynthesis, metabolism and sterol function in plants. The latter, unlike cholesterol, are alkylated in position 24 and are the precursors of plant steroid hormones, the brassinolides. Studies carried out in his laboratory show that these sterols are structuring agents of plant cell membranes and in particular of the plasma membrane.Isabelle Schuller, Alain Milon, Yoichi Nakatani, Guy Ourisson, Anne-Marie Albrecht, Pierre Benveniste et Marie-Andrée Hartmann, « Differential effects of plant sterols on water permeability and on acyl chain ordering of soybean phosphatidyl choline bilayers », Proc. Natl. Acad. Sci.
|
|
In enzymology, a cycloartenol 24-C-methyltransferase () is an enzyme that catalyzes the chemical reaction :S-adenosyl-L-methionine + cycloartenol \rightleftharpoons S-adenosyl-L-homocysteine + (24R)-24-methylcycloart-25-en-3beta-ol Thus, the two substrates of this enzyme are S-adenosyl methionine and cycloartenol, whereas its two products are S-adenosylhomocysteine and (24R)-24-methylcycloart-25-en-3beta-ol. 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:cycloartenol 24-C-methyltransferase. This enzyme is also called sterol C-methyltransferase.
|
|
Momordica dioica as the average nutritional value per 100 g edible fruit was found to contain 84.1% moisture, 7.7 g carbohydrate, 3.1 g protein, 3.1 g fat, 3.0 g fiber and 1.1 g minerals. It also contained small quantities of essential vitamins like ascorbic acid, carotene, thiamin, riboflavin and niacin. It also content protein in the leaves and dry weight of aerial plant parts remained higher in male as compared to female defruited, and monoecious plants. From Momordica dioica fruit isolated 6-methyl tritriacont-50on-28-of and 8- methyl hentracont-3-ene along with the known sterol pleuchiol.
|
|
Myxobacteria are known for their ability to produce diverse natural products as secondary metabolites, though terrestrial members of the group are much better characterized than marine myxobacteria. Several types of unusual secondary metabolites have been isolated from E. salina cultures. One class, given the name salimyxins, is composed of incisterols, a rare class of natural products with a spotty phylogenetic distribution; production of any type of sterol is rare for prokaryotic organisms. Another class of natural products isolated from E. salina was termed enhygrolides and are chemically related to compounds known from cyanobacteria of the genus Nostoc.
|
|
Owades was born in Manhattan, the son of Jewish parents, and raised in the Bronx. His father, Shmuel, was a dressmaker. In 1939 he graduated from City College of New York (undergraduate), followed by New York University Tandon School of Engineering (Master's and PhD in biochemistry, 1944, 1950), with a dissertation on cholesterol titled Sterol Sulphates: A Study of αCholesterylene and Other Decomposition Products. After wartime work for the US Navy, he went on to Fleischmann's Yeast, Schwarz Laboratories in Mount Vernon, New York (where he taught the Schwarz Brewing Course), and Rheingold Breweries in Brooklyn, where he became Vice President–Technical Director.
|
|
The side effects of ketoconazole are sometimes harnessed in the treatment of non-fungal conditions. While ketoconazole blocks the synthesis of the sterol ergosterol in fungi, in humans, at high dosages (>800 mg/day), it potently inhibits the activity of several enzymes necessary for the conversion of cholesterol to steroid hormones such as testosterone and cortisol. Specifically, ketoconazole has been shown to inhibit cholesterol side-chain cleavage enzyme, which converts cholesterol to pregnenolone, 17α-hydroxylase and 17,20-lyase, which convert pregnenolone into androgens, and 11β-hydoxylase, which converts 11-deoxycortisol to cortisol. All of these enzymes are mitochondrial cytochrome p450 enzymes.
|
|
Rising levels of sterols increase the susceptibility of the reductase enzyme to ER-associated degradation (ERAD) and proteolysis. Helices 2-6 (total of 8) of the HMG-CoA reductase transmembrane domain are thought to sense increased cholesterol levels (direct sterol binding to the SSD of HMG-CoA reductase has not been demonstrated). Lysine residues 89 and 248 can become ubiquinated by ER-resident E3 ligases. The identity of the multiple E3 ligases involved in HMG-CoA degradation is controversial, with suggested candidates being AMFR, Trc8, and RNF145 The involvement of AMFR and Trc8 has been contested.
|
|
Lecithin–cholesterol acyltransferase (LCAT, also called phosphatidylcholine–sterol O-acyltransferase) is an enzyme that converts free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of a lipoprotein particle, eventually making the newly synthesized HDL spherical and forcing the reaction to become unidirectional since the particles are removed from the surface. The enzyme is bound to high-density lipoproteins (HDLs) (alpha-LCAT) and LDLs (beta-LCAT) in the blood plasma. LCAT deficiency can cause impaired vision due to cholesterol corneal opacities, anemia, and kidney damage. It belongs to the family of phospholipid:diacylglycerol acyltransferases.
|
|
As one of the major phytosterols, stigmasterol is included among sterol compounds in the diet having potential to reduce the risk of cardiovascular diseases. Consumption of 2 grams per day of plant sterols is associated with a reduction in blood LDL cholesterol of 8-10%, possibly lowering cardiovascular disease risk. As a factor in cellular processes of plants, stigmasterol may have roles in plant stress responses, metabolism, and enzymes involved in biosynthesis of plant cell membranes. Stigmasterol has also been shown to exert anti- angiogenic and anti-cancer effects via the downregulation of TNF-alpha and VEGFR-2.
|
|
Glucose signaling also induces CYP7A1 gene transcription by epigenetic regulation of the histone acetylation status. Glucose induction of bile acid synthesis have an important implication in metabolic control of glucose, lipid, and energy homeostasis under normal and diabetic conditions. CYP7A1-rs3808607 and APOE isoform are associated with the extent of reduction in circulating LDL cholesterol in response to PS(define PS, Plant Sterol?) consumption and could serve as potential predictive genetic markers to identify individuals who would derive maximum LDL cholesterol lowering with PS consumption. Genetic variations in CYP7A1 influence its expression and thus may affect the risk of gallstone disease and gallbladder cancer.
|
|
Although PPARγ and C/EBPα are master regulators of adipogenesis, other transcription factors function in the progression of differentiation. Adipocyte determination and differentiation factor 1 (ADD1) and sterol regulatory element binding protein 1 (SREBP1) can activate PPARγ by the production of an endogenous PPARγ ligand or directly promote the expression of PPARγ. cAMP-responsive element binding protein promotes differentiation, while the activation of PPARγ and C/EBPα is also responsive to negative regulation. T-cell factor/lymphoid enhancer-binding factor (TCF/LEF), GATA2/3, retinoic acid receptor α, and SMAD6/7 don't affect the expression of C/EBPβ and C/EBPδ but inhibit the induction of PPARγ and C/EBPα.
|
|
Common puffball, releasing spores in a burst by compressing the body The puffball grows in fields, gardens, and along roadsides, as well as in grassy clearings in woods. It is edible when young and the internal flesh is completely white, although care must be taken to avoid confusion with immature fruit bodies of poisonous Amanita species. L. perlatum can usually be distinguished from other similar puffballs by differences in surface texture. Several chemical compounds have been isolated and identified from the fruit bodies of L. perlatum, including sterol derivatives, volatile compounds that give the puffball its flavor and odor, and the unusual amino acid lycoperdic acid.
|
|
As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol- regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
Momordol or 1-hydroxy-1,2-dimethyl-2-[8′,10′-dihydroxy-4′,7′-dimethyl-11′-hydroxy methyl- trideca]-3-ethyl-cyclohex-5-en-4-one is a chemical compound with formula , found in the fresh fruit of the bitter melon (Momordica charantia).Sabira Begum, Mansour Ahmed, Bina S. Siddiqui, Abdullah Khan, Zafar S. Saify, and Mohammed Arif (1997), Triterpenes, a sterol and a monocyclic alcohol from Momordica charantia. Phytochemistry, volume 44, issue 7, pages 1313-1320 The compound is an oily liquid, soluble in ethyl acetate and methanol but not in pure chloroform or petrol. It was isolated in 1997 by S. Begum and others.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
407-413 were isolated, transformed plants with gain or loss of function were selected and identified. Advances in the knowledge of the regulation of the biosynthesis of sterols and their derivatives (esters, glucosides) as well as their functions have been obtained.Pascaline Ullmann, Pierrette Bouvier-Navé et Pierre Benveniste, « Regulation by phospholipids and kinetic studies of plant membrane-bound UDP- glucose sterol ß-D-glucosyltransferase », Plant Physiol., 85, 1987, p. 51-55 Work focused on three enzyme systems: epoxide of squalene triterpene synthase,Tania Husselstein-Muller, Hubert Schaller, and Pierre Benveniste, « Molecular cloning and expression in yeast of 2,3-oxidosqualene-triterpenoid cyclases from Arabidopsis thaliana », Plant Mol. Biol.
|
|
In enzymology, a Delta24-sterol reductase () is an enzyme that catalyzes the chemical reaction :5alpha-cholest-7-en-3beta-ol + NADP+ \rightleftharpoons 5alpha-cholesta-7,24-dien-3beta-ol + NADPH + H+ Thus, the two substrates of this enzyme are 5alpha-cholest-7-en-3beta-ol and NADP+, whereas its 3 products are 5alpha-cholesta-7,24-dien-3beta-ol, NADPH, and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is sterol:NADP+ Delta24-oxidoreductase. This enzyme is also called lanosterol Delta24-reductase. This enzyme participates in biosynthesis of steroids.
|
|
De novo lipogenesis (DNL) is the process by which carbohydrates (primarily, especially after a high-carbohydrate meal) from the circulation are converted into fatty acids, which can by further converted into triglycerides or other lipids. Acetate and some amino acids (notably leucine and isoleucine) can also be carbon sources for DNL. Normally, de novo lipogenesis occurs primarily in adipose tissue. But in conditions of obesity, insulin resistance, or type 2 diabetes de novo lipogenesis is reduced in adipose tissue (where carbohydrate-responsive element-binding protein (ChREBP) is the major transcription factor) and is increased in the liver (where sterol regulatory element-binding protein 1 (SREBP-1c) is the major transcription factor).
|
|
Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb).
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol- regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol- regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol- regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
|
|
The equivalent ability and safety of plant sterols and plant stanols to lower cholesterol continues to be a hotly debated topic. Plant sterols and stanols, when compared head to head in clinical trials, have been shown to equally reduce cholesterol levels. A meta-analysis of 14 randomized, controlled trials comparing plant sterols to plant stanols directly at doses of 0.6 to 2.5 g/day showed no difference between the two forms on total cholesterol, LDL cholesterol, HDL cholesterol, or triglyceride levels. Trials looking at high doses (> 4 g/day) of plant sterols or stanols are very limited, and none have yet to be completed comparing the same high dose of plant sterol to plant stanol.
|
|
The biosynthesis of isoprenoids There is a relationship between MKD and the interleukin 1beta (IL-Iβ). There is an increased IL-1β secretion and mevalonate kinase deficiency in MKD is most likely mediated by defective protein prenylation (Prenylation refers to addition of hydrophobic residues to proteins) ] and non-sterol isoprenoids, such as farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) are coupled to a target protein, which affects the activity and the cellular location. In a human monocytic MKD model it was found that the deficiency of GGPP leads to overproduction of IL-1β and defective prenylation of RhoA. This causes an increased level of Rac1 and PKB which was affecting the GTPases and B7-Glycoproteins.
|
|
UV-Vis spectroscopy analysis of olive oil samples in an Italian laboratory The detection of olive oil adulteration is often complicated with no single test that can accomplish the task. A battery of tests is employed to determine olive oil authenticity and identity of the adulterant. Included in this testing regime is the determination of free acidity, peroxide value, UV extinction, fatty acid composition, sterol composition, triglyceride composition, wax content, steroidal hydrocarbons, and the Bellier test. Methods employing chromatography/mass spectrometry and spectroscopy are often used to detect adulteration of olive oil These methods can be very expensive, time consuming, and results are often incomplete, since components added/substituted can not always be identified.
|
|
Amorolfine (or amorolfin), is a morpholine antifungal drug that inhibits Δ14-sterol reductase and cholestenol Δ-isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membranes. Marketed as Curanail, Loceryl, Locetar, and Odenil, amorolfine is commonly available in the form of a nail lacquer, containing 5% amorolfine hydrochloride as the active ingredient. It is used to treat onychomycosis (fungal infection of the toe- and fingernails). Amorolfine 5% nail lacquer in once-weekly or twice-weekly applications has been shown in two studies to be between 60% and 71% effective in treating toenail onychomycosis; complete cure rates three months after stopping treatment (after six months of treatment) were 38% and 46%.
|
|
When AMPK phosphorylates acetyl- CoA carboxylase 1 (ACC1) or sterol regulatory element-binding protein 1c (SREBP1c), it inhibits synthesis of fatty acids, cholesterol, and triglycerides, and activates fatty acid uptake and β-oxidation. AMPK stimulates glucose uptake in skeletal muscle by phosphorylating Rab-GTPase- activating protein TBC1D1, which ultimately induces fusion of GLUT1 vesicles with the plasma membrane. AMPK stimulates glycolysis by activating phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2/3 and activating phosphorylation of glycogen phosphorylase, and it inhibits glycogen synthesis through inhibitory phosphorylation of glycogen synthase. In the liver, AMPK inhibits gluconeogenesis by inhibiting transcription factors including hepatocyte nuclear factor 4 (HNF4) and CREB regulated transcription coactivator 2 (CRTC2).
|
|
Insulin acting via the sterol regulatory element binding protein-1c (SREBP1c) is thought to be the most important direct activator of glucokinase gene transcription in hepatocytes. SREBP1c is a basic helix-loop-helix zipper (bHLHZ) transactivator. This class of transactivators bind to the "E box" sequence of genes for a number of regulatory enzymes. The liver promoter in the first exon of the glucokinase gene includes such an E box, which appears to be the principal insulin-response element of the gene in hepatocytes. It was previously thought that SREBP1c must be present for transcription of glucokinase in hepatocytes however, it was recently shown that glucokinase transcription was carried out normally in SREBP1c knock out mice.
|
|
Pierre Benveniste is a former student of the European School of Chemistry in Strasbourg (present name) (1962). After a PhD (Use of tissue cultures for the study of natural products) carried out under the direction of Professors Léon Hirth and Guy Ourisson and obtained in 1967, he turned his attention to the study of sterol biosynthesis in plants. In charge of research at the CNRS until 1970, he was appointed lecturer in 1970 and then professor in 1975 at the University of Strasbourg. He first became director of the ERA n° 487 of the CNRS then director of the isoprenoids department of the Institute of Plant Molecular Biology (IBMP) of the CNRS.
|
|
Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in fungi, and named for ergot, the common name of members of the fungal genus Claviceps from which ergosterol was first isolated. Ergosterol is a component of yeast and other fungal cell membranes, serving many of the same functions that cholesterol serves in animal cells. Its specificity in higher fungi is thought to be related to the climatic instabilities (highly varying humidity and moisture conditions) encountered by these organisms in their typical ecological niches (plant and animal surfaces, soil). Thus, despite the added energy requirements of ergosterol synthesis (if compared to cholesterol), ergosterol is thought to have evolved as a nearly ubiquitous, evolutionarily advantageous fungal alternative to cholesterol.
|
|
Ceragenins, or cationic steroid antimicrobials (CSAs), are synthetically- produced, small-molecule chemical compounds consisting of a sterol backbone with amino acids and other chemical groups attached to them. These compounds have a net positive charge that is electrostatically attracted to the negative-charged cell membranes of certain viruses, fungi and bacteria. CSAs have a high binding affinity for such membranes (including Lipid A) and are able to rapidly disrupt the target membranes leading to rapid cell death. While CSAs have a mechanism of action that is also seen in antimicrobial peptides, which form part of the body's innate immune system, they avoid many of the difficulties associated with their use as medicines.
|
|
In enzymology, a Delta14-sterol reductase () is an enzyme that catalyzes the chemical reaction :4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ \rightleftharpoons 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+ Thus, the two substrates of this enzyme are 4,4-dimethyl-5alpha- cholesta-8,24-dien-3beta-ol and NADP+, whereas its 3 products are 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, NADPH, and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol:NADP+ Delta14-oxidoreductase. This enzyme participates in biosynthesis of steroids.
|
|
Meanwhile, Stockton arrives at the facility, with the others in tow, and enters the facility. While this is going on, Thor is revealed to be undergoing a form of genetic mutation and needs the sterols from the brainstem to stay alive, to which he sprouts a pincer from his mouth and uses it to take the bound Alex's sterol, killing him. Stockton and the others split up after Wendy sees the facility's experiments and becomes upset with her father's involvement and she storms off; Mark goes off to find her while Stockton goes to find the scientists and Scott stays in the rec room. Stockton finds Larry's body and heads back to get the others out of the facility.
|
|
Several carotenoids are responsible for the various colours of the cap, tubes, and stem, while variegatic and xerocomic acid cause the bluing reaction that occurs with tissue injury. The composition of the volatile flavour compounds of Suillellus luridus consists largely of linoleic acid, with smaller proportions of 1-butanol, 3-methyl-1-butanol, pentadecanoic acid, palmitic acid, linoleic acid methyl ester, and heptadecanoic acid. Pyrazine compounds might be responsible for the characteristic odour of the dried mushroom. The predominant sterol present in the fruit bodies is ergosterol, with smaller amounts of closely related derivative compounds. The main fatty acids of the mushroom include linoleic acid (53.4% of total fatty acids), oleic acid (24.1%), and palmitic acid (10.2%).
|
|
Unifying properties of putative EMC clients are the presence of unusually hydrophilic transmembrane domains containing charged residues. However, mechanistic detail of how the EMC assists in orienting and inserting such problematic transmembrane domains is lacking. In many cases, evidence implicating the EMC in the biogenesis of a certain protein consists of co-depletion when individual subunts of the EMC are disrupted. A number of putative EMC clients are listed below, but the manner in which the EMC engages them and whether they directly or indirectly depend on the EMC merits further investigation: Loss of EMC function destabilises the enzyme sterol-O-acyltransferase 1 (SOAT1) and, in conjunction with overlooking the biogenesis of squalene synthase (SQS), helps to maintain cellular cholesterol homeostasis.
|
|
The nuclear lamina lies on the inner surface of the inner nuclear membrane (INM), where it serves to maintain nuclear stability, organize chromatin and bind nuclear pore complexes (NPCs) and a steadily growing list of nuclear envelope proteins (purple) and transcription factors (pink). Nuclear envelope proteins that are bound to the lamina include nesprin, emerin, lamina-associated proteins 1 and 2 (LAP1 and LAP2), the lamin B receptor (LBR) and MAN1. Transcription factors that bind to the lamina include the retinoblastoma transcriptional regulator (RB), germ cell-less (GCL), sterol response element binding protein (SREBP1), FOS and MOK2. Barrier to autointegration factor (BAF) is a chromatin-associated protein that also binds to the nuclear lamina and several of the aforementioned nuclear envelope proteins.
|
|
David Gottlieb (1911–1982), a professor of plant pathology at the University of Illinois at Urbana-Champaign (1946–1982), was a pioneer in the field of fungal physiology and antibiotics for plants. Gottlieb is best known for isolation in the 1940s of the strain of Streptomyces from which chloramphenicol was developed, for his mentoring in the field, and for his editorial work.Editor for the Annual Review of Phytopathology, 1969-1974 He used plant-pathogenic fungi in studies of sterol biosynthesis, respiration, aging, spore germination, and the mechanism of action of antifungal antibiotics. Gottlieb discovered or co-discovered several new antibiotics in addition to chloramphenicol, including filipin, levomycin, and tetrin, and he described the mechanism of action and biosynthesis of several of these and other antibiotics.
|
|
Phytosterols have a long history of safe use, dating back to Cytellin, the pharmaceutical preparation of phytosterols marketed in the US from 1954-82. Phytosterol esters have generally recognized as safe (GRAS) status in the US. Phytosterol-containing functional foods were subject to postlaunch monitoring after being introduced to the EU market in 2000, and no unpredicted side effects were reported. A potential safety concern regarding phytosterol consumption is in patients with phytosterolaemia, a rare genetic disorder which results in a 50- to 100-fold increase in blood plant sterol levels and is associated with rapid development of coronary atherosclerosis. Phytosterolaemia has been linked to mutations in the ABCG5/G8 proteins which pump plant sterols out of enterocytes and hepatocytes into the lumen and bile ducts, respectively.
|
|
Production of mycotoxins or secondary metabolites by P. digitatum has not been observed although this species has been shown to be toxic to both shrimp and chicken embryos. With respect to fungicidal tolerance, there are known strains of P. digitatum resistant to various commonly used fungicides. Reports have been made concerning fungicides thiabendazole, benomyl, imazalil, sodium-o-phenylphenate as well as fungistatic agent, biphenyl, with no prior treatment required in the case of biphenyl. The mechanism of P. digitatum resistance to imazalil is suggested to lie in the over-expression of the sterol 14α-demethylase (CYP51) protein caused by a 199 base-pair insertion into the promoter region of the CYP51 gene and/or by duplications of the CYP51 gene.
|
|
The taxon name farnesiana is named after Odoardo Farnese (1573–1626) of the notable Italian Farnese family which, after 1550, under the patronage of cardinal Alessandro Farnese, maintained some of the first private European botanical gardens in Rome, the Farnese Gardens, in the 16th and 17th centuries. This acacia was first described from these gardens; imported to Italy from Santo Domingo, in what is now the Dominican Republic. Analysis of essences of the floral extract from this plant, long used in perfumery, resulted in the name for the sesquiterpene biosynthetic chemical farnesol, found as a basic sterol precursor in plants, and cholesterol precursor in animals. The name huisache of Mexico and Texas is derived from Nahuatl and means "many thorns,".
|
|
In enzymology, a propanoyl-CoA C-acyltransferase () is an enzyme that catalyzes the chemical reaction :3alpha,7alpha,12alpha-trihydroxy-5beta- cholanoyl-CoA + propanoyl-CoA \rightleftharpoons CoA + 3alpha,7alpha,12alpha- trihydroxy-24-oxo-5beta-cholestanoyl-CoA Thus, the two substrates of this enzyme are 3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoyl-CoA and propanoyl- CoA, whereas its two products are CoA and 3alpha,7alpha,12alpha- trihydroxy-24-oxo-5beta-cholestanoyl-CoA. 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 3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoyl-CoA:propanoyl-CoA C-acyltransferase. Other names in common use include peroxisomal thiolase 2, sterol carrier protein-, SCP, and PTE-2 (ambiguous).
|
|
Pregnenolone succinate (; brand names Panzalone, Formula 405; also known as pregnenolone hemisuccinate or pregn-5-en-3β-ol-20-one 3β-(hydrogen succinate)) is a synthetic pregnane steroid and an ester of pregnenolone which is described as a glucocorticoid and anti-inflammatory drug and has been patented and marketed as a topical medication in the form of a cream for the treatment of allergic, pruritic, and inflammatory dermatitis. It has also been described as a non-hormonal sterol, having neurosteroid activity, and forming a progesterone analogue via dehydrogenation. In addition to its glucocorticoid effects, pregnenolone succinate has been found to act as a negative allosteric modulator of the GABAA receptor and a positive allosteric modulator of the NMDA receptor similarly to pregnenolone sulfate.
|
|
Cytotoxicity caused by ion channel formation is commonly seen in the world of bacteria. While eukaryotic cells are generally less vulnerable to channel- forming toxins because of their larger volume and stiffer, sterol-containing membranes, several eukaryotic channel-forming toxins have been seen to sidestep these obstacles by forming especially large, stable ion channels or anchoring to sterols in the cell membrane. Neurons are particularly vulnerable to channel-forming toxins because of their reliance on maintenance of strict Na+, K+, and Ca2+ concentration gradients and membrane potential for proper functioning and action potential propagation. Leakage caused by insertion of an ion channel such as Aβ rapidly alters intracellular ionic concentrations, resulting in energetic stress, failure of signaling, and cell death.
|
|
Insig deficiency in mice caused a marked buildup of cholesterol precursors in skin associated with a marked increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase protein and hair and skin defects corrected by topical simvastatin, an inhibitor of reductase. REV- ERBalpha participates in the circadian modulation of sterol regulatory element-binding protein (SREBP) activity, and thereby in the daily expression of SREBP target genes involved in cholesterol and lipid metabolism. This control is exerted via the cyclic transcription of Insig2, encoding a trans- membrane protein that sequesters SREBP proteins to the endoplasmic reticulum membranes and thereby interferes with the proteolytic activation of SREBPs in Golgi membranes. REV-ERBalpha also participates in the cyclic expression of cholesterol-7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in converting cholesterol to bile acids.
|
|
Due to the significant correlations identified between hypoxia, fungal infections, and negative clinical outcomes, the mechanisms by which A. fumigatus adapts in hypoxia is a growing area of focus for novel drug targets. Two highly characterized sterol- regulatory element binding proteins, SrbA and SrbB, along with their processing pathways, have been shown to impact the fitness of A. fumigatus in hypoxic conditions. The transcription factor SrbA is the master regulator in the fungal response to hypoxia in vivo and is essential in many biological processes including iron homeostasis, antifungal azole drug resistance, and virulence. Consequently, the loss of SrbA results in an inability for A. fumigatus to grow in low iron conditions, a higher sensitivity to anti-fungal azole drugs, and a complete loss of virulence in IPA (invasive pulmonary aspergillosis) mouse models.
|
|
Studies provide evidence through monolayer measurements, condensing properties, and nearly identical gel to liquid-crystalline phase transition temperatures (Tm) to the host membranes that the presence of these bonds do not play a major role or interfere in the recognition or packing formation of the modeled membranes in the presence of ethanol. The disulfide bonds, diacylglycerol bonds, and similar sterol framework are only present to mimic the physical properties of DSPC, DPPC, and cholesterol as well as aid in the monomer exchanging processes to form exchangeable dimers. The exchangeable lipids undergo a monomer interchanging process through the disulfide bridges in which they either mix ideally, homogenously, or heterogeneously. Their interactions are measured by the equilibrium constant (K) which will be described in further detail under the significance of results section.
|
|
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.
|
|
Afterwards, the hydrazone is deprotonated by lithium diisopropylamide (LDA) to form an azaenolate, which reacts with alkyl halides or other suitable electrophiles to give alkylated hydrazone species with the simultaneous generation of a new chiral center. Finally, the alkylated ketone or aldehyde can be regenerated by ozonolysis or hydrolysis. Enders' SAMP/RAMP Hydrazone Alkylation Reaction This reaction is a useful technique for asymmetric α-alkylation of ketones and aldehydes, which are common synthetic intermediates for medicinally interesting natural products and other related organic compounds. These natural products include (-)-C10-demethyl arteannuin B, the structural analog of antimalarial artemisinin, the polypropionate metabolite (-)-denticulatin A and B isolated from Siphonaria denticulata, zaragozic acid A, a potent inhibitor of sterol synthesis, and epothilone A and B, which have been proven to be very effective anticancer drugs.
|
|
" But Nobel laureate Joseph Goldstein (1985), who is still very active in the laboratory at the University of Texas at Dallas, was not ready to give up his work on the molecular genetics of blood lipids."Journal of Clinical Investigation Interview Film Annex In 1993, their postdoctoral trainees, Wang Xiaodong and Michael Briggs, purified the Sterol Regulatory Element-Binding Proteins (SREBPs), a family of membrane-bound transcription factors. Since 1993, Goldstein, Brown, and their colleagues have described the unexpectedly complex machinery that proteolytically releases the SREBPs from membranes, thus allowing their migration to the nucleus where they activate all the genes involved in the synthesis of cholesterol and fatty acids. The machinery for generating active SREBPs is tightly regulated by a negative feedback mechanism, which explains how cells maintain the necessary levels of fats and cholesterol in the face of varying environmental circumstances.
|
|
Julian also announced the synthesis, starting with the cheap and readily available pregnenolone (synthesized from the soybean oil sterol stigmasterol) of the steroid cortexolone (also known as Reichstein's Substance S, and most often referred as 11-Deoxycortisol), a molecule that differed from cortisone by a single missing oxygen atom; and possibly 17α-hydroxyprogesterone and pregnenetriolone, which he hoped might also be effective in treating rheumatoid arthritis, but unfortunately they were not. On April 5, 1952, biochemist Durey Peterson and microbiologist Herbert Murray at Upjohn published the first report of a fermentation process for the microbial 11α-oxygenation of steroids in a single step (by common molds of the order Mucorales). Their fermentation process could produce 11α-hydroxyprogesterone or 11α-hydroxycortisone from progesterone or Compound S, respectively, which could then by further chemical steps be converted to cortisone or 11β-hydroxycortisone (cortisol).
|
|
In enzymology, a sterol 14-demethylase () is an enzyme that catalyzes the chemical reaction :obtusifoliol + 3 O2 \+ 3 NADPH + 3 H+ \rightleftharpoons 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + formate + 3 NADP+ \+ 4 H2O The 4 substrates of this enzyme are obtusifoliol, O2, NADPH, and H+, whereas its 4 products are 4alpha-methyl-5alpha- ergosta-8,14,24(28)-trien-3beta-ol, formate, NADP+, and H2O. Ergosterol Although lanosterol 14α-demethylase is present in a wide variety of organisms, this enzyme is studied primarily in the context of fungi, where it plays an essential role in mediating membrane permeability. In fungi, CYP51 catalyzes the demethylation of lanosterol to create an important precursor that is eventually converted into ergosterol. This steroid then makes its way throughout the cell, where it alters the permeability and rigidity of plasma membranes much as cholesterol does in animals.
|
|
Cholesterol is biosynthesized in a series of more than 25 separate enzymatic reactions that initially involves three successive condensations of acetyl-CoA units to form the six-carbon compound 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA). This is reduced to mevalonate and then converted in a series of reactions to the isoprenes that are building-blocks of squalene, the immediate precursor to sterols, which cyclizes to lanosterol (a methylated sterol) and further metabolized to cholesterol. A number of early attempts to block the synthesis of cholesterol resulted in agents that inhibited late in the biosynthetic pathway between lanosterol and cholesterol. A major rate-limiting step in the pathway is at the level of the microsomal enzyme that catalyzes the conversion of HMG CoA to mevalonic acid, and that has been considered to be a prime target for pharmacologic intervention for several years.
|
|
X-ray crystallography demonstrated the sterol molecules were flat, not as proposed by the German team led by Windaus. In 1932, Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance. The informal academic collaboration between the team members Robert Benedict Bourdillon, Otto Rosenheim, Harold King, and Kenneth Callow was very productive and led to the isolation and characterization of vitamin D. At this time, the policy of the Medical Research Council was not to patent discoveries, believing the results of medical research should be open to everybody. In the 1930s, Windaus clarified further the chemical structure of vitamin D. In 1923, American biochemist Harry Steenbock at the University of Wisconsin demonstrated that irradiation by ultraviolet light increased the vitamin D content of foods and other organic materials.
|
|
Percy's research at Glidden changed direction in 1940 when he began work on synthesizing progesterone, estrogen, and testosterone from the plant sterols stigmasterol and sitosterol, isolated from soybean oil by a foam technique he invented and patented.U.S. Patent 2,273,046 At that time clinicians were discovering many uses for the newly discovered hormones. However, only minute quantities could be extracted from hundreds of pounds of the spinal cords of animals. In 1940 Julian was able to produce 100 lb of mixed soy sterols daily, which had a value of $10,000 ($ today) as sex hormones. Julian was soon ozonizing 100 pounds daily of mixed sterol dibromides. The soy stigmasterol was easily converted into commercial quantities of the female hormone progesterone, and the first pound of progesterone he made, valued at $63,500 ($ today), was shipped to the buyer, Upjohn,Bryan A. Wilson and Monte S. Willis, "Percy Lavon Julian, Pioneer of Medicinal Chemistry Synthesis" , Lab Medicine.
|
|
Through systematic and careful labeling- and enzyme activity studies in the 1980s and 90s, he was able to demonstrate several previously unknown biochemical pathways for oil production in seeds and which later proved to be true for plant cells in general. Later in his career, Stymne focused on studying the biochemical processes involved in the biosynthesis of exotic fatty acids, an area where Sten have had great impact by increasing the knowledge of how specialized acyltransferases and phospholipases are essential for the enrichment of exotic fatty acids in the oil. Furthermore, Stymne's group could identify and describe a whole new plant family of enzymes (PDATs) previously identified only in animals and responsible for transferring fatty acids between phospholipids and diacylglycerol molecules which play an important role in oil synthesis not only in plants but at all higher organisms. Stymne's group was also the first to clone and characterize plant genes for membrane lipid synthesis (LPCATs) and synthesis of sterol esters (PSAT).
|
|
SNX8 protein regulates cholesterol levels as an activator of the SREBPs (Sterol Regulatory Element Binding Proteins), which is a family of transcription factors that control the expression of enzymes needed for the synthesis and uptake of fatty acids, endogenous cholesterol, triacylglycerides and phospholipids; this results in an overall regulation of intracellular lipid homeostasis. Although its precise mechanism of action remains unknown, data suggests that SNX8 produces changes in cholesterol distribution through regulation of the SREBP transcriptional activity by modulating intracellular traffic events rather than by interacting with proteins of the SREBP pathway like INSIG or SREBP cleavage-activating protein (SCAP). For example, it is unclear if SNX8 has a direct participation in the transport of SREBP pathway components or if it regulates endosomal and lysosomal compartimentalisation through the production of cholesterol cargoes. This last possibility is supported by the fact that the ability of altering membrane curvature is shared by some proteins of the SNXs family.
|
|
The molecular mechanisms regulating the absorption of dietary sterols in the body are poorly understood, and as sitosterolemia is a rare autosomal recessively inherited lipid metabolic disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols, studies have focused on the molecular basis of sitosterolemia to shed light on important principles concerning intestinal sterol absorption as well as cholesterol secretion into bile. In 1998, sitosterolemia (STSL) locus has been mapped to the short arm of human chromosome 2 (2p21) after studying 10 well-characterized families with this disorder. Subsequently, the STSL locus has been further localized to a less than 2 centimorgans (cM) region. In 2001, The STSL locus was found to be comprises two genes, ABCG5 and ABCG8, encoding 2 members of the ABC- transporter family, named sterolin-1 and sterolin-2, respectively, Sterolin-2, discovered after sterolin-1, is located <400 base pair (bp) upstream of sterolin-1 in the opposite orientation.
|
|