People with one copy of this version and one of the faster-metabolizing type are considered to be moderate metabolizers, whereas people with two copies of the slow-metabolizing variant are, of course, slow caffeine metabolizers.
|
|
The particular enzyme that we're studying is involved in metabolizing chemotherapy drugs.
|
|
They looked at genetic variants related to metabolizing alcohol in more than 4,000 kids.
|
|
Some researchers also believe that sweeteners may interfere with the body's mechanisms for metabolizing sugar.
|
|
"This stored form is called glycogen and utilizing or metabolizing it utilizes water," she says.
|
|
They're metabolizing, so they're giving you life energy, and it helps to raise your overall vibes.
|
|
"There are concerns with women's differential metabolizing of MDMA combined with low body mass index," she says.
|
|
By metabolizing thousands of cat photos, for instance, a neural network can learn to recognize a cat.
|
|
Metabolizing fructose is a plant strategy, and the researchers were surprised to see it in a mammal.
|
|
Mr. Haidt said the Facebook effect was "catalyzing or amplifying" a tendency already there (not "metabolizing or amplifying").
|
|
America, stunned and divided, appears incapable of metabolizing all we're learning about the man in the White House.
|
|
Ethanol can prevent the body from metabolizing the methanol into deadly toxins, buying patients time for treatments like dialysis.
|
|
Kanye West vacillates between being ham-fistedly provocative and metabolizing the backlash he receives from his outlandish behavior into content.
|
|
Well, I'll tell you what you're looking at—the early stages of my body metabolizing sustenance into nutrients, that's what.
|
|
"If you eat a large amount of concentrated calories, you're going to generate heat from metabolizing them," Ms. Nestle said.
|
|
Stool is the end product of our gut metabolizing our food, and it consists of non-absorbed material, microbes, and water.
|
|
The entire system for metabolizing philanthropic gifts, particularly private ones, into academic research is a poorly illuminated pile of broken guardrails.
|
|
When most adult killifish encounter dioxin, this receptor's signaling pathway revs to life in the hope of metabolizing the chemical invader.
|
|
A baby with galactosemia, a metabolic disorder that prevents the baby from metabolizing galactose, will die or suffer brain damage from breastfeeding.
|
|
That kind of goodwill needs time to accrue—the kind of time that's hard to find in today's fast-metabolizing culture-consumption cycle.
|
|
The Centers for Disease Control and Prevention notes that women have a harder time metabolizing alcohol because of their body structure and chemistry.
|
|
In summary:Type O: This, the oldest blood type, is well suited to metabolizing animal protein, fat, and cholesterol, but not grains or dairy.
|
|
Metabolizing this period in her life and putting it to song, St. Vincent made a hyperactive drum machine and synth-bass pop dream.
|
|
I'm not fasting per se but I am definitely at the point in this diet where I've began metabolizing my own brain for energy.
|
|
The loss of tissue lowers the amount of water the body is able to hold, and water plays an important role in metabolizing alcohol.
|
|
"It's by far the most selective compound, compared to other SSRIs that affect other neurotransmitters and interact with more metabolizing enzymes," says its creator.
|
|
Alcohol receptors exist in the stomach and the liver, so by removing so much of the stomach, people lose the first pass at metabolizing alcohol.
|
|
Methane is a potent greenhouse gas, and these microbes are preventing enormous quantities of it from reaching the atmosphere by metabolizing runoff from the seeps.
|
|
They in turn were replaced at depths down to 80 cm by a unique group of bacteria that survive by metabolizing methane as a food source.
|
|
Even if you have everything you need to make that metabolizing green smoothie, you might not realize it because the ingredients are hiding behind microwaveable pizzas.
|
|
He remained a lifelong student of the highest caliber: co-teaching with philosophers, metabolizing esoteric doctrines, even directing the Committee on Social Thought at the University of Chicago.
|
|
In addition, the Japanese have a higher prevalence of genetic variations that make them slower at metabolizing alcohol, and the results may not be generalizable to other populations.
|
|
And Latin America has had a great deal of difficulty metabolizing it, because the Caribbean is English-speaking, French-speaking, Dutch-speaking, Creoles, and all of those languages.
|
|
In 2013 the FDA had to tell women to cut their dose in half because it turned out they were metabolizing the active ingredient twice as slowly [as men].
|
|
The simple answer is the same one it always is: Things are bad, and people are anxious about whatever ongoing horrors are metabolizing in geopolitics, the environment, and capitalism.
|
|
"Individuals genetically predisposed to consuming greater amounts of coffee are likely metabolizing caffeine quickly, and so to achieve and maintain the 'caffeine buzz,' they need to consume more," she said.
|
|
Two years ago, scientists at the University of Maryland discovered that, in mice, a byproduct of the body metabolizing ketamine was what really exerted the antidepressant effect, not ketamine itself.
|
|
Scientists found a gene that makes us fast or slow at metabolizing the stimulant, and discovered that the rapid set enjoys far greater health and performance gains from ingesting it.
|
|
The authors reported that a mutation of FADS2, a gene involved in metabolizing fatty acids, is more common in northern than southern populations, indicating a diet richer in animal content.
|
|
And it was a metabolizing of the idea, in this moment, that you could have safely in the game that you could have fun with and then be done afterwards.
|
|
Eating the root raw or unprocessed means eating cyanide and metabolizing it, which in turn can affect thyroid hormones and damage nerve cells in the brain relating to movement, Spencer said.
|
|
Moreland's songs are populated by figures in comparable states of tumult: broken men metabolizing loss, trying to figure out what love means and how much anyone can reasonably expect of it.
|
|
The gut microbiome, the roughly 10 trillion to 100 trillion bacteria and other microorganisms that live in the digestive tract, contributes to health by synthesizing vitamins, metabolizing drugs and fighting pathogens.
|
|
She points to the conflicting Viking experiments on Mars in the 1970s, when a lander found some support for metabolizing microbes but no evidence for organic molecules, as a prime example.
|
|
"Big plastics cannot enter into or be absorbed into tiny fmicroorganism, so bacteria typically do not degrade polyurethane, even if they are capable of metabolizing little bits and pieces of it," he said.
|
|
They lived in extreme environments, at least some of them — hot springs, salty lakes, sewage — and some had unusual metabolic habits, such as metabolizing without oxygen and, as the Times account said, producing methane.
|
|
The mom of two had increased her protein intake while preparing for a bodybuilding competition, but doctors discovered too late that she had a rare disorder that prevented her body from properly metabolizing the nutrient.
|
|
If a sulfur-metabolizing ectoplasmic alien were to be found in the vicinity of Alpha Centauri, say, there's a good chance that it, too, would possess autoregulatory loops for resisting changes in its bodily functions.
|
|
The moon's transition to Aquarius offers a bit of reprieve from the bitter medicine you've been metabolizing under the surface, especially when it harmoniously connects with the sun and Mercury in curiously-inclined Gemini on Thursday.
|
|
The research suggests that the calories we burn from digesting, absorbing and metabolizing the nutrients in the food we eat -- known as diet-induced thermogenesis -- are influenced by our circadian system, and are lower at 8 p.m.
|
|
"Because our brain tastes sweet and perceives the sweet taste when we&aposre having artificial sweetener metabolically, our body acts like we&aposre metabolizing sugar, so you may crave more sweets if you have that," says Gandhi.
|
|
But the experiment's early results are just now emerging, and they seem to show that the combined emissions of humans and their daily activities—cooking, cleaning, metabolizing—are more interesting, and potentially more lethal, than anyone had imagined.
|
|
For example, research suggests that the calories we burn from digesting, absorbing and metabolizing the nutrients in the food we eat -- known as diet-induced thermogenesis -- is influenced by our circadian system and is lower at 2003 p.m.
|
|
And, if it turns out your CBD product of choice is preventing your body from properly metabolizing another medication, your doctor will know if that's solved by adjusting your dose or if you need to stop using CBD altogether.
|
|
Only after her death did her family learn that Hefford, the mother of a 7-year-old girl and a 5-year-old boy, had a rare genetic disorder that prevented her body from properly metabolizing her high-protein diet.
|
|
That's why his guilt over his perceived role in Chuck's suicide seems to be eating him alive, where Jimmy seems to be metabolizing it — if he's feeling it at all — in a way that will lead to his self-destruction.
|
|
And despite the notion that eating more often means more opportunities to burn calories, thanks to the energy involved in digesting, absorbing and metabolizing food's nutrients, research suggests that doing so does not appear to significantly enhance metabolism or total calories burned.
|
|
So the more metabolizing we do, the more we build up these free radicals, the more these nightmare particles bump around in our cells and smash up proteins, and the accumulation of those free radicals, one could say is what aging is.
|
|
They found that, astonishingly, the microorganism is capable of metabolizing CO2, meaning it can scoop up the carbon it releases when it breaks down cellulose—re-absorbing its own waste produce, and preventing it from adding to the total gaseous CO2 in the environment.
|
|
With hangover results that could speak for themselves, their hope is that people will feel confident enough to have a pop and see whether the idea of a biotech enhanced probiotic that's pumping out extra alcohol-metabolizing enzymes stands up to several pints of lager and a few chasers (or not).
|
|
She dissects the culture the country has been metabolizing for the past decades, and the consumerist messages we receive day in and day out on social media (which are, of course, no longer framed as brands selling us products, but instead about us being brands, and actual brands being lifestyles).
|
|
There are a number of factors that are responsible for these differences, which include the different enzyme systems for metabolizing the medications, the different abilities to excrete the medication, the presence of concurrent psychotropic and nonpsychotropic medications in our bodies and the different lengths of time different medications stay in one's body.
|
|
To start, it's important to mention that I generally don't recommend juicing to clients since many juices contain high amounts of fructose sugar that can disrupt hunger hormones and fast metabolizing glucose that can send your blood sugar on a crazy roller coaster ride — the exact opposite of how I want my clients to feel.
|
|
In countering the amyloid theory, which had become the conventional wisdom and the basis for most research funding, Dr. Roses maintained that dementia in Alzheimer's patients resulted from a gene variation that inhibits mitochondria, or mini-organs within a cell, from metabolizing glucose and oxygen, a process necessary to fuel neurons in the brain.
|
|
That said, when one steps back from the pummeling chaos of the daily news cycle and gains a vantage overlooking the battlefield, one begins to observe signs of hope that our system, and the institutions and values that give it vitality, may be up to the challenge, that it is indeed metabolizing this difficult moment as it was designed to.
|
|
Certainly, some species may not appear to need as much activity as much as others (consider relatively slow-metabolizing species like Galapagos tortoises, African lions that naturally sleep on average 16 hours each day, or bullfrogs who are ambush predators and owe much of their adaptive success in catching prey to being able to sit still and wait for long periods of time).
|
|
"Even if someone feels like the caffeine causes them to feel more awake and less sluggish, they still need to be aware that the alcohol is still metabolizing in the same way and on the same timeframe as if they haven't had any caffeine ... which means that its effects can still be potentially dangerous," said Melissa Majumdar, a registered dietitian and spokesperson for the Academy of Nutrition and Dietetics.
|
|
Microfossils indicate the presence of cyanobacteria, green and purple sulfur bacteria, methane-producing archaea or bacteria, sulfate-metabolizing bacteria, methane-metabolizing archaea or bacteria, iron-metabolizing bacteria, nitrogen-metabolizing bacteria, and anoxygenic photosynthetic bacteria.
|
|
As the biofilm biomass changes from Carbon metabolizing to nitrifying, a visual colour change from grey/beige to brown can be seen which is illustrated by the adjacent photo. Biofilm color transition from grey/beige to brown, left to right, indicates slow transition from Carbon metabolizing bacteria to Nitrogen metabolizing bacteria. Courtesy of KEE Process Ltd. Biofilms, which are biological growths that become attached to the discs, assimilate the organic materials (measured as BOD5) in the wastewater.
|
|
While setipiprant mildly induces the drug metabolizing enzyme CYP3A4 in vitro, the interaction appears to not be clinically relevant.
|
|
It is likely, although not yet shown, that these mouse and pig 20-HETE metabolizing pathways also occur in humans.
|
|
Thus, Oxidation to galactonate serves as an alternate pathway for metabolizing galactose. This oxidative pathway renders accumulated galactonate less harmful than accumulated galactitol.
|
|
Research suggests the reason for this relationship is due to a functional tradeoff, with the enzymes that metabolize estradiol instead metabolizing/detoxifying tobacco toxins.
|
|
Pyrethroids can be combined with the synergist piperonyl butoxide, a known inhibitor of key microsomal cytochrome P450 enzymes from metabolizing the pyrethroid, which increases its efficacy (lethality).
|
|
Debrisoquine is a derivative of guanidine. It is an antihypertensive drug similar to guanethidine. Debrisoquine is frequently used for phenotyping the CYP2D6 enzyme, a drug-metabolizing enzyme.
|
|
Apparently, the N-domain does not have a big role in controlling blood pressure but it seems to be the principal metabolizing enzyme for AcSDKP, a natural haemoregulatory hormone.
|
|
When drugs are taken orally, they enter the gut lumen to be absorbed in the small intestine and sometimes, in the stomach. In order for drugs to be absorbed, they must pass through the epithelial cells that line the lumen wall before they can enter the hepatic portal circulation to be distributed systemically in blood circulation. Drugs are metabolized by drug-specific metabolizing enzymes in the epithelial cells. Metabolizing enzymes transform these drugs into metabolites.
|
|
The following oxygenase enzymes may be responsible for metabolizing PUFA to resolvins: 15-lipoxygenase-1 (i.e. ALOX15), possibly 15-lipoxygenase-2 (i.e. ALOX15B), 5-lipoxygenase (i.e. ALOX5), cyclooxygenase-2 (i.e.
|
|
The adaptive response is manifested as the induction of xenobiotic metabolizing enzymes. Evidence of this response was first observed from the induction of cytochrome P450, family 1, subfamily A, polypeptide 1 (Cyp1a1) resultant from TCDD exposure, which was determined to be directly related to activation of the Ahr signaling pathway. The search for other metabolizing genes induced by Ahr ligands, due to the presence of DREs, has led to the identification of an "Ahr gene battery" of Phase I and Phase II metabolizing enzymes consisting of CYP1A1, CYP1A2, CYP1B1, NQO1, ALDH3A1, UGT1A2 and GSTA1. Presumably, vertebrates have this function to be able to detect a wide range of chemicals, indicated by the wide range of substrates Ahr is able to bind and facilitate their biotransformation and elimination.
|
|
The primary purpose for drug metabolism is to detoxify, inactivate, solubilize and eliminate these drugs.Pandit Introduction to Pharmaceutical Sciences As a result, the amount of the drug in its original form that reaches systemic circulation is reduced due to this first-pass metabolism. Furanocoumarins (see section above) irreversibly inhibit a metabolizing enzyme cytochrome P450 3A4 (CYP3A4). CYP3A4 is a metabolizing enzyme for almost 50% of drugs, and is found in the liver and small intestinal epithelial cells.
|
|
Such pathogens may have alternative methods for metabolizing phytoalexins. In addition, many microbial species have been found to have the ability to detoxify pisatin, but the most virulent strains have the highest rate of demethylation.
|
|
In other studies, D.P. Agarwal and colleagues associated race-based variations in the activity alcohol-metabolizing enzymes with the occurrence of alcohol flush reactions to alcohol and alcoholic beverages in certain Asian populations.Hum Genet. 1979 Oct 2;51(3):331-4Am J Hum Genet. 1983 Jul;35(4):769-72 This early work is the basis for further studies that have defined not only many alcohol-induced flush reactions but also many alcohol-induced respiratory reactions as due to racially associated genetic differences in alcohol-metabolizing enzymes.
|
|
CYP3A4 is a metabolizing enzyme for almost 50% of drugs, and is found in the liver and small intestinal epithelial cells. As a result, many drugs are affected. Inhibition of enzymes can have two different effects, depending on whether the drug is either #metabolized by the enzyme to an inactive metabolite, or #activated by the enzyme to an active metabolite. In the first instance, inhibition of drug-metabolizing enzymes results in elevated concentrations of an active drug in the body, which may cause adverse effects.
|
|
In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity, thereby protecting the cells from reactive oxygen species and the products of peroxidation.
|
|
In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity thereby protecting the cells from reactive oxygen species and the products of peroxidation.
|
|
Idiomarina tyrosinivorans is a Gram-negative, strictly aerobic, non-spore- forming, curved-rod-shaped, tyrosine-metabolizing and motile bacterium from the genus of Idiomarina which has been isolated from water off the river Pingtung in Taiwan.
|
|
Additional in vitro and in vivo studies of omadacycline metabolism, disposition, and drug interactions show that omadacycline is metabolically stable (i.e., it does not undergo significant biotransformation) and neither inhibits nor interacts with metabolizing enzymes or transporters.
|
|
Studies into the metabolism and excretion processes for the molecule have shown that the compound undergoes two primary phase II biotransformations to form the corresponding glucuronide and sulfate. Different cell types have a bias towards which metabolite gets produced, with the human hepatoma cell line primarily metabolizing to the corresponding sulfate, and hepatocytes metabolizing to both the glucuronide and the sulfate compounds. Additionally, phase I metabolism produces various hydroxylated metabolites of BPF, with the main metabolites being meta-hydroxylated BPF, ortho-hydroxylated BPF and dihydroxybenzophenone (DHB). These metabolic pathways are P450 dependent.
|
|
In phase-II metabolizing includes glucuronidation and sulfation of the mycoestrogen compound. Glucuronidation is the major phase II metabolic pathway. The transferase UGT (5'-diphosphate glucuronosyltransferase) adds a glucuronic acid group sourced from uridine 5'-diphosphate glucuronic acid (UDPGA).
|
|
Genetic variants of N-acetyltransferase were also discovered in his laboratory. Furthermore, Meyer contributed to the molecular mechanism by which drugs activate transcription factors such as nuclear receptors and thereby regulate the expression of drug metabolizing enzymes and drug transporters.
|
|
The gene Apolipoprotein B, which is involved in transporting and metabolizing fat soluble molecules in the blood, is expressed in the yolk sac and fetal liver. Within the neurula in Xenopus laevis, development genes Xwnt-3 and Xwnt-4 are present.
|
|
Mitochondrial membrane potential is hyperpolarized to prevent voltage-sensitive permeability transition pores (PTP) from triggering of apoptosis. The ketogenic diet is being investigated as an adjuvant therapy for some cancers, including glioma, because of cancer's inefficiency in metabolizing ketone bodies.
|
|
Ketoacidosis is most commonly the result of complete insulin deficiency in type 1 diabetes or late-stage type 2 diabetes. Ketone levels can be measured in blood, urine or breath and are generally between 0.5 and 3.0 millimolar (mM) in physiologic ketosis, while ketoacidosis may cause blood concentrations greater than 10 mM. Trace levels of ketones are always present in the blood and increase when blood glucose reserves are low and the liver shifts from primarily metabolizing carbohydrates to metabolizing fatty acids. This occurs during states of increased fatty acid oxidation such as fasting, starvation, carbohydrate restriction, or prolonged exercise.
|
|
The aim of this genetic recombination in the laboratory is to develop a yeast strain that efficiently produces ethanol. However, the effectiveness of D-xylose metabolizing laboratory strains do not always reflect their metabolism abilities on raw xylose products in nature. Since D-xylose is mostly isolated from agricultural residues such as wood stocks then the native or genetically altered yeasts will need to be effective at metabolizing these less pure natural sources. Varying expression of the XR and XDH enzyme levels have been tested in the laboratory in the attempt to optimize the efficiency of the D-xylose metabolism pathway.
|
|
There is one generation per year. The larvae feed on Heracleum sphondylium, Pastinaca sativa and Apium nodiflorum. They feed on the flowers and developing seeds, defending their territory by enclosing an umbel in silk, while safely metabolizing the ingested furocoumarins.May Berenbaum, et al.
|
|
Pomegranate juice inhibits the action of the drug metabolizing enzymes CYP2C9 and CYP3A4. However, as of 2014, the currently available literature does not appear to indicate a clinically relevant impact of pomegranate juice on drugs that are metabolized by CYP2C9 and CYP3A4.
|
|
Zafirlukast is an inhibitor of the hepatic drug- metabolizing enzyme cytochrome P450 family 3 subfamily A member 4 (CYP3A4). Zafirlukast may increase the concentration of drugs that are metabolized through CYP3A4, such as the anticoagulant medication warfarin and the antiepileptic drugs phenytoin and carbamazepine.
|
|
Pyrococcus abyssi is a hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent in the North Fiji Basin at . It is anaerobic, sulfur- metabolizing, gram-negative, coccus-shaped and highly motile. Its optimum growth temperature is . Its type strain is GE5 (CNCM I-1302).
|
|
In addition to bacteria, aquatic plants also eliminate nitrogen waste by metabolizing ammonia and nitrate. When plants metabolize nitrogen compounds, they remove nitrogen from the water by using it to build biomass that decays more slowly than ammonia- driven plankton already dissolved in the water.
|
|
Clinafloxacin inhibits multiple CYP450 drug metabolizing enzymes, especially CYP1A2. Clinafloxacin has induced the accumulation of CYP1A2 substrates, including theophylline, at therapeutic doses. This can also affect the metabolism of caffeine, another CYP1A2 substrate. Caffeine consumption must be limited while taking clinafloxacin to prevent caffeine accumulation and overdose.
|
|
This prolonged duration is thought to be caused by the compounding effects of absorbing and metabolizing breakfast carbohydrates during this period. Both the dawn phenomenon and its extended period have been shown to be significantly more difficult to control when a patient's HbA1c is greater than 7%.
|
|
The opposite is also true (e.g., enzyme inhibition). However, in cases where an enzyme is responsible for metabolizing a pro-drug into a drug, enzyme induction can speed up this conversion and increase drug levels, potentially causing toxicity. Various physiological and pathological factors can also affect drug metabolism.
|
|
Although it bears homology to some drug-metabolizing cytochrome P450s, it is unknown whether the enzyme is also involved in xenobiotic metabolism. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Alternate splicing of this gene results in three transcript variants encoding different isoforms.
|
|
This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may play a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2013].
|
|
The Mal regulon are set of genes excited by catabolite activator protein commonly known as CAP. The genes code for maltose metabolizing enzymes. The genes encoding the enzymes are non-contiguous, and regulated by multiple promoters. Mal regulon is regulated by catabolite activator protein in a novel manner.
|
|
Like many other Astragalus species, this plant accumulates selenium from the soil. It has also been shown to harbor a selenium-metabolizing Bacillus species in its seed pods.Lindblow-Kull, C., A. Shrift, and R. L. Gherna. (1982). Aerobic, selenium-utilizing Bacillus isolated from the seeds of Astragalus crotalariae.
|
|
15-lipoxygenase type 2 (ALOX15B) strongly prefers arachidonic acid over linoleic acid and in consequence is relatively poor in metabolizing linoleic acid to 13(S)-HpODE (which is then converted to 13(S)-HODE) compared to 15-lipoxygenase 1; nonetheless, it can contribute to the production of these metabolites.
|
|
Ectonucleotidases consist of families of nucleotide metabolizing enzymes that are expressed on the plasma membrane and have externally oriented active sites. These enzymes metabolize nucleotides to nucleosides. The contribution of ectonucleotidases in the modulation of purinergic signaling depends on the availability and preference of substrates and on cell and tissue distribution.
|
|
At least some species of carp are able to survive for months with practically no oxygen (for example under ice or in stagnant, scummy water) by metabolizing glycogen to form lactic acid which is then converted into ethanol and carbon dioxide. The ethanol diffuses into the surrounding water through the gills.
|
|
Consequently, mammals are intolerant to MFA. However, few Australian species (e.g. brush-tailed possum) show a level of tolerance to fluoroacetate by metabolizing it using glutathione-s-transferase Mead, R. J., Oliver, A. J., & King, D. R. (1979). Metabolism and defluorination of fluoroacetate in the brush-tailed possum (Trichosurus vulpecula).
|
|
4 (June 1951). It inspired an APA, MYOB and an Avoidist Movement which avoided amounting to anything. Tenets are those implied by the root word. Lee Hoffman explains that three types of avoidism are distinguished: # pure # applied # active (or Activist) In pure avoiding, one avoids everything except eating, breathing and metabolizing.
|
|
This is mainly done by Type I enzymes such as mixed function oxidases. These enzymes use O2 to catalyze a reaction and convert acetamiprid into more polar metabolites. This makes it easier to excrete the compounds because the compounds become more hydrophilic. Phase I enzymes form the first step in metabolizing the compound.
|
|
Chronic phenytoin use has been associated with decreased bone density and increased bone fractures. Phenytoin induces metabolizing enzymes in the liver. This leads to increased metabolism of vitamin D, thus decreased vitamin D levels. Vitamin D deficiency, as well as low calcium and phosphate in the blood cause decreased bone mineral density.
|
|
AHRR is known to inhibit the aryl hydrocarbon receptor, which is important to metabolizing harmful chemicals. The resultant increase in AHRR expression could lead to a decrease in the body's ability to break down carcinogens, increasing the risk of cancer. F2RL3 is known to be involved in blood clotting and the inflammation response.
|
|
Rubredoxins are a class of low-molecular-weight iron-containing proteins found in sulfur-metabolizing bacteria and archaea. Sometimes rubredoxins are classified as iron-sulfur proteins; however, in contrast to iron-sulfur proteins, rubredoxins do not contain inorganic sulfide. Like cytochromes, ferredoxins and Rieske proteins, rubredoxins participate in electron transfer in biological systems.
|
|
As a short chain fatty acid, butyric acid is fully ionized near neutral pH. In nature, the cation associated with butyrate is unknown or unimportant to the metabolizing enzymes. Butyrates are important as food for cells lining the mammalian colon (colonocytes). Without butyrates for energy, colon cells undergo autophagy (self digestion) and die.
|
|
For example, a patient could possess a genetic defect in a drug metabolizing enzyme in the cytochrome P450 superfamily. While most individuals will possess the effective metabolizing machinery, a person with a defect will have a difficult time trying to clear the drug from their system. Thus, the drug will accumulate within the blood to higher-than-expected concentrations, reaching a MTC at a dose that would otherwise be considered normal for the average person. In other words, in a person that is intolerant to a medication, it is possible for a dose of 10 mg to "feel" like a dose of 100 mg, resulting in an overdose—a "normal" dose can be a "toxic" dose in these individuals, leading to clinically significant effects.
|
|
Cholesterol is susceptible to oxidation and easily forms oxygenated derivatives called oxysterols. Three different mechanisms can form these: autoxidation, secondary oxidation to lipid peroxidation, and cholesterol-metabolizing enzyme oxidation. A great interest in oxysterols arose when they were shown to exert inhibitory actions on cholesterol biosynthesis. This finding became known as the “oxysterol hypothesis”.
|
|
19-hydroxyeicosatetraenoic acid and/or 20-hydroxyeicosatetranoic acid, take on epoxygease activity in converting DHA primarily to 19,20-EDP isomers (see epoxyeicosatrienoic acid). The CYP450 epoxygenases capable of metabolizing DHA to EDPs are widely distributed in organs and tissues such as the liver, kidney, heart, lung, pancreas, intestine, blood vessels, blood leukocytes, and brain.
|
|
Some endoliths have extremely long lives. In August 2013, researchers reported evidence of endoliths in the ocean floor, perhaps millions of years old, with a generation time of 10,000 years.Bob Yirka Aug 29, 2013 These are slowly metabolizing and not in a dormant state. Some Actinobacteria found in Siberia are estimated to be half a million years old.
|
|
The genome of R. palustris consists of a variety of genes that are responsible for biodegradation. R. palustris can metabolize lignin and acids found in degrading plant and animal waste by metabolizing carbon dioxide. In addition, it can degrade aromatic compounds found in industrial waste. This bacterium is an efficient biodegradation catalyst in both aerobic and anaerobic environments.
|
|
Downregulation refers to the decrease in the number of receptor sites. This can be accomplished by metabolizing bound FSHR sites. The bound FSH-receptor complex is brought by lateral migration to a "coated pit," where such units are concentrated and then stabilized by a framework of clathrins. A pinched-off coated pit is internalized and degraded by lysosomes.
|
|
Downregulation refers to the decrease in the number of receptor sites. This can be accomplished by metabolizing bound LHCGR sites. The bound LCGR complex is brought by lateral migration to a coated pit, where such units are concentrated and then stabilized by a framework of clathrins. A pinched-off coated pit is internalized and degraded by lysosomes.
|
|
Dictyoglomus is a genus of bacterium, given its own subphylum, called the Dictyoglomi. This organism is extremely thermophilic, meaning it thrives at extremely high temperatures. It is chemoorganotrophic, meaning it derives energy by metabolizing organic molecules. This organism is of interest because it elaborates an enzyme, xylanase, which digests xylan, a heteropolymer of the pentose sugar xylose.
|
|
During this period she survives by metabolizing the proteins of her flight muscles. As the eggs hatch and the ants develop, they spend that time, about two to three months, tending to the queen of their colony. They will continue helping in the colony until they are a month old. Older workers forage for food and defend the colony.
|
|
Cupriavidus necator has gone through a series of name changes. In the first half of the 20th century, many micro-organisms were isolated for their ability to use hydrogen. Hydrogen-metabolizing chemolithotrophic organisms were clustered into the group Hydrogenomonas. C. necator was originally named Hydrogenomonas eutrophus because it fell under the Hydrogenomonas classification and was “well nourished and robust”.
|
|
It is also capable of metabolizing estrogen and progesterone. AKR1C3 may play an important role in the development of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.
|
|
An alternative to geochemical injection would instead be to physically store carbon dioxide in containers with algae or bacteria that could degrade the carbon dioxide. It would ultimately be ideal to exploit the carbon dioxide metabolizing bacterium Clostridium thermocellum in such theoretical storage containers. Using this bacteria would prevent overpressurization of such theoretical carbon dioxide storage containers.
|
|
The cytochrome p450 system is found in nearly all life forms and is responsible for processing pheromones and steroids and also metabolizing insecticides, drugs, mutagens, and carcinogens. The p450 system allows Drosophila to metabolize and detoxify the secondary compounds that the cacti use as a function of herbivore defense in order to viably use the plant as a host.
|
|
However, only a fraction of the total concentration of ALDH3A1 in the cornea is used for metabolizing aldehydes. This observation has sparked multiple investigations of ALDH3A1's role beyond aldehyde metabolism. Although the full scope of ALDH3A1's function is yet to be firmly established, there is strong evidence suggesting that ALDH3A1 serves to maintain the cellular redox balance as well as the structural integrity and transparency of the cornea. One study elucidates that ALDH3A1 not only indirectly protects the cornea from UVR induced oxidative stress by metabolizing aldehydes, but also protects the tissue directly, by competitively absorbing UVR in a “suicide response” that reduces damage to other proteins of the cornea In fact, 50% percent of the UVR that the cornea is exposed to is absorbed by ADLH3A1.
|
|
Since OXCT1 functions in metabolizing ketone bodies, it has been proposed to promote tumor growth by providing tumor cells with an additional energy source. Therefore, ketone inhibitors may prove effective in treating patients experiencing recurring and metastatic tumors. A proteomics study identified OXCT1 to be one of 16 proteins upregulated in carcinoma HepG2 cells treated with Platycodin D, an anti-cancer agent.
|
|
The drug metabolizing enzymes primarily responsible for rabeprazole's metabolism are CYP2C19 and CYP3A4. However, rabeprazole is mainly metabolized through non-enzymatic reduction to a thioether metabolite. Some of rabeprazole's metabolites include the following: a thioether carboxylic acid metabolite, a thioether glucuronide metabolite, and a sulfone metabolite. The most common metabolites excreted in the urine are the mercapturic acid conjugate and carboxylic acid.
|
|
Mesotherms have two basic characteristics: # Elevation of body temperature via metabolic production of heat. # Weak or absent metabolic control of a particular body temperature. The first trait distinguishes mesotherms from ectotherms, the second from endotherms. For instance, endotherms, when cold, will generally resort to shivering or metabolizing brown fat to maintain a constant body temperature, leading to higher metabolic rates.
|
|
Several microorganisms in the lake have been isolated and studied, with their genomes sequenced. Among these is Exiguobacterium sp. strain 17 which was first isolated in Laguna Socompa; it possesses a number of genes involved in metabolizing arsenic and other toxic compounds and protecting and repairing the genome. Other strains from Laguna Socompa whose genomes have been sequenced are Salinivibrio sp.
|
|
Aldehyde oxidase (AO) is a metabolizing enzyme, located in the cytosolic compartment of tissues in many organisms. AO catalyzes the oxidation of aldehydes into carboxylic acid, and in addition, catalyzes the hydroxylation of some heterocycles. It can also catalyze the oxidation of both cytochrome P450 (CYP450) and monoamine oxidase (MAO) intermediate products. AO plays an important role in the metabolism of several drugs.
|
|
Unlike ciprofloxacin, levofloxacin does not appear to deactivate the drug metabolizing enzyme CYP1A2. Therefore, drugs that use that enzyme, like theophylline, do not interact with levofloxacin. It is a weak inhibitor of CYP2C9, suggesting potential to block the breakdown of warfarin and phenprocoumon. This can result in more action of drugs like warfarin, leading to more potential side effects, such as bleeding.
|
|
Aromatase is highly expressed in adipose tissue and the brain, and is also expressed significantly in skeletal muscle. 3α-HSD is highly expressed in skeletal muscle as well. Natural AAS like testosterone and DHT and synthetic AAS are analogues and are very similar structurally. For this reason, they have the capacity to bind to and be metabolized by the same steroid-metabolizing enzymes.
|
|
Like all protein-rich foods, spirulina contains the essential amino acid phenylalanine (2.6-4.1 g/100 g), which should be avoided by people who have phenylketonuria, a rare genetic disorder that prevents the body from metabolizing phenylalanine, which then builds up in the brain, causing damage. Spirulina contaminated with microcystins has various potential toxicity, especially to children, including liver damage, shock and death.
|
|
Tyrosine metabolic pathway. Fumarylacetoacetate hydrolase (FAH) is shown to be nonfunctional, leading to the accumulation of maleylacetoacetate (MAA) and succinylacetoacetate (SAA), the later of which is converted to succinylacetone (SA). Fumarylacetoacetate hydrolase (FAH) is the final enzyme in the tyrosine metabolic pathway. The mutation of FAH enzyme results in nonfunctional FAH in all cells expressing this gene and thus metabolizing tyrosine is impaired.
|
|
This is supported by findings that BLT2 is abnormally expressed in many human cancers that concurrently overexpress these arachidonic acid metabolizing pathways viz., follicular thyroid adenoma, Renal cell carcinoma, urinary bladder Transitional cell carcinoma, esophagus squamous cell carcinoma, colon adenocarcinoma, the Serous cystadenocarcinoma type of ovarian cancer, and uterine cervical carcinoma. Other studies have implicated BLT2 in these and other types of cancer as follows.
|
|
In these compounds, the three hydroxyl groups of glycerol are each esterified, typically by different fatty acids. Because they function as an energy store, these lipids comprise the bulk of storage fat in animal tissues. The hydrolysis of the ester bonds of triglycerides and the release of glycerol and fatty acids from adipose tissue are the initial steps in metabolizing fat.van Holde and Mathews, pp. 630–31.
|
|
This bacterium grows in environments of 10 to 44 degrees Celsius with optimal growth at 37 degrees and prefers a pH balance of 9.5, similar to that of baking soda, hand soap, or a solution of household bleach in water. S. americana is capable of metabolizing D-glucose, fructose, maltose, sucrose, starch and D-mannitol and has as its waste H2, acetate, ethanol and formate.
|
|
This can mean that there are three possible variations in the two compartment model, which still do not cover all possibilities.Milo Gibaldi, Donald Perrier. FarmacocinéticaReverté 1982 pages 1–10. , 9788429155358 This model may not be applicable in situations where some of the enzymes responsible for metabolizing the drug become saturated, or where an active elimination mechanism is present that is independent of the drug's plasma concentration.
|
|
All organisms are constantly exposed to compounds that they cannot use as foods and would be harmful if they accumulated in cells, as they have no metabolic function. These potentially damaging compounds are called xenobiotics. Xenobiotics such as synthetic drugs, natural poisons and antibiotics are detoxified by a set of xenobiotic-metabolizing enzymes. In humans, these include cytochrome P450 oxidases, UDP-glucuronosyltransferases, and glutathione S-transferases.
|
|
The EETs have a wide range of activities including the promotion of certain types of cancers (see epoxyeicosatetraenoic acid#cancer). CYP3A4 promotes the growth of various types of human cancer cell lines in culture by producing (±)-14,15-epoxyeicosatrienoic acids which stimulate these cells to grow. The cytochrome P450 is also reported to have fatty acid monooxgenase activity for metabolizing arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE).
|
|
Affected drugs typically have an auxiliary label saying "Do not take with grapefruit" on the container, and the interaction is elaborated upon in the package insert. People are also advised to ask their physician or pharmacist about drug interactions. The effects are caused by furanocoumarins (and, to a lesser extent, flavonoids). These chemicals inhibit key drug metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4).
|
|
Diauxie is a Greek word coined by Jacques Monod to mean two growth phases. The word is used in English in cell biology to describe the growth phases of a microorganism in batch culture as it metabolizes a mixture of two sugars. Rather than metabolizing the two available sugars simultaneously, microbial cells commonly consume them in a sequential pattern, resulting in two separate growth phases.
|
|
Cypermethrin is very toxic to cats which cannot tolerate the therapeutic doses for dogs. This is associated with UGT1A6 deficiency in cats, the enzyme responsible for metabolizing cypermethrin. As a consequence, cypermethrin remains much longer in the cat's organs than in dogs or other mammals and can be fatal in large doses. In male rats cypermethrin was shown to exhibit a toxic effect on the reproductive system.
|
|
Measurements of a biomarker of ethanol breakdown suggest that they may be metabolizing it by a pathway that is not used as heavily by humans. Their ability to ingest high amounts of alcohol is hypothesized to have been an evolutionary adaptation in the phylogenic tree. However, how pen-tailed treeshrews benefit from this alcohol ingestion or what consequences of consistent high blood alcohol content might factor into their physiology is unclear.
|
|
While Trichonympha has been found to be capable of metabolizing cellulose without any bacterial symbionts, it still needs a wide variety of bacterial ectosymbionts and endosymbionts to survive. It has been found that Trichonympha and various endosymbiotic bacteria may be evolving together (cospeciating), suggesting that the symbiosis is a vital part of both the bacterial and Trichonympha cell’s success. The exact composition and function of Trichonympha’s symbionts is still being investigated.
|
|
An additional 10% is excreted in urine as metabolites. Urinary excretion is virtually complete 24 hours after administration. Dose adjustment is required in the elderly and in those with renal impairment. Ciprofloxacin is weakly bound to serum proteins (20-40%), but is an inhibitor of the drug-metabolizing enzyme cytochrome P450 1A2, which leads to the potential for clinically important drug interactions with drugs metabolized by that enzyme.
|
|
Academic Press. 3rd. p.700. There are many kinds of invertebrates, vertebrates and plants that carry out coprophagy. By doing so, all these detritivores contribute to decomposition and the nutrient cycles. They should be distinguished from other decomposers, such as many species of bacteria, fungi and protists, which are unable to ingest discrete lumps of matter, but instead live by absorbing and metabolizing on a molecular scale (saprotrophic nutrition).
|
|
They now comprise the plasma membrane noradrenaline transporter (NAT or NET), the classical uptake1, and the analogous dopamine transporter (DAT); the plasma membrane extraneuronal monoamine transporter or organic cation transporter 3 (EMT or SLC22A3), Iversen's uptake2; and the vesicular monoamine transporter (VMAT) with two isoforms. Transporters and intracellular enzymes such as monoamine oxidase operating in series constitute what the pharmacologist Ullrich Trendelenburg at the University of Würzburg called metabolizing systems.
|
|
Electric bacteria are forms of bacteria that directly consume and excrete electrons at different energy potentials without requiring the metabolization of any sugars or other nutrients. Shewanella and Geobacter are two known types of electric bacteria. This form of life appears to be especially adapted to low-oxygen environments. Most life forms require an oxygen environment in which to release the excess of electrons which are produced in metabolizing sugars.
|
|
These catalogs may eventually lead to more complete wiring diagrams of diseases. The KEGG DRUG database contains active ingredients of approved drugs in Japan, the US, and Europe. They are distinguished by chemical structures and/or chemical components and associated with target molecules, metabolizing enzymes, and other molecular interaction network information in the KEGG pathway maps and the BRITE hierarchies. This enables an integrated analysis of drug interactions with genomic information.
|
|
The typical concentration of naringin in grapefruit juice is around 400 mg/l. The reported LD50 of naringin in rodents in 2000 mg/kg. Naringin inhibits some drug- metabolizing cytochrome P450 enzymes, including CYP3A4 and CYP1A2, which may result in drug-drug interactions. Ingestion of naringin and related flavonoids can also affect the intestinal absorption of certain drugs, leading to either an increase or decrease in circulating drug levels.
|
|
Hydrogen is produced by hydrogenases and nitrogenases enzymes in many microorganisms, some of which are being studied for their potential for biofuel production. These H2-metabolizing enzymes are found in all three domains of life, and out of known genomes over 30% of microbial taxa contain hydrogenase genes. Fermentation produces H2 from organic matter as part of the anaerobic microbial food chain via light-dependent or light- independent pathways.
|
|
At this depth, there is no light and little oxygen, so Balnearium lithotrophicum is an obligate anaerobe bacterium. An obligate anaerobe is a bacterium that cannot survive in the presence of oxygen that is found in the atmosphere. Balnearium lithotrophicum is identified as a chemolithoautotroph, “eater of rock”, that reduces strictly inorganic compounds in order to survive. It gets its energy from metabolizing hydrogen from the black smoker chimney.
|
|
Marketed as a safer alternative to barbiturate anxiolytics, meprobamate (Miltown, Equanil) was commonly used to relieve anxiety in the late 1950s and 1960s. Like barbiturates, therapeutic doses produce sedation and significant overdoses may be fatal. In the US, meprobamate has generally been replaced with benzodiazepines while the drug is now withdrawn in many European countries and Canada. The muscle relaxant carisoprodol has anxiolytic effects by metabolizing to meprobamate.
|
|
When the study of gut flora began, it was thought to have three key roles: direct defense against pathogens, fortification of host defense by its role in developing and maintaining the intestinal epithelium and inducing antibody production there, and metabolizing otherwise indigestible compounds in food; subsequent work discovered its role in training the developing immune system, and yet further work focused on its role in the gut-brain axis.
|
|
Phosphorylation of a hexose such as glucose often limits it to a number of intracellular metabolic processes, such as glycolysis or glycogen synthesis. This is because phosphorylated hexoses are charged, and thus more difficult to transport out of a cell. In patients with essential fructosuria, metabolism of fructose by hexokinase to fructose-6-phosphate is the primary method of metabolizing dietary fructose; this pathway is not significant in normal individuals.
|
|
Biotin is an important component of enzymes involved in metabolizing fats and carbohydrates, influencing cell growth, and affecting amino acids involved in protein synthesis. Biotin assists in various metabolic reactions involving the transfer of carbon dioxide. It may also be helpful in maintaining a steady blood sugar level. Biotin is often recommended as a dietary supplement for strengthening hair and nails, though scientific data supporting these outcomes are weak.
|
|
Acylsugars are also classified as amphiphiles which provide a supplementary source of water in plants by reducing the surface tension of dew, allowing it to be absorbed more easily. Acylsugars are also used in pesticides, food additives, cosmetics and personal care products, antibiotics, and anti inflammatory medications. Therefore acylsugars have been the focus of studies aiming to discover successful breeding crop techniques and synthetic methods of metabolizing acylsugars.
|
|
Measurements of a biomarker of ethanol breakdown suggest that they may be metabolizing it by a pathway that is not used as heavily by humans. Their ability to ingest high amounts of alcohol is hypothesized to have been an evolutionary adaptation in the phylogenic tree. However, how pen-tailed treeshrews benefit from this alcohol ingestion or what consequences of consistent high blood alcohol content might factor into their physiology is unclear.
|
|
5-HT normally dampens aggression in animals and humans. Mice missing specific genes for 5-HT were observed to be more aggressive than normal mice and were more rapid and violent in their attacks. Other studies have been focused on neurotransmitters. Studies of a mutation in the neurotransmitter metabolizing enzyme monoamine oxidase A (MAO-A) have been shown to cause a syndrome that includes violence and impulsivity in humans.
|
|
Nature has evolved numerous enzymes which metabolize oxylipins into secondary products, many of which possess strong biological activity. Of special importance are the cytochrome P450 enzymes in animals, including CYP5A1 (thromboxane synthase), CYP8A1 (prostacyclin synthase), and the CYP74 family of hydroperoxide-metabolizing enzymes in plants, lower animals and bacteria. In the plant and animal kingdoms the C18 and C20 polyenoic fatty acids, respectively, are the major precursors of oxylipins.
|
|
As a result, many drugs are impacted by consumption of citrus juice. When the metabolizing enzyme is inhibited, less of the drug will be metabolized by it in the epithelial cells. A decrease in drug metabolism means more of the original form of the drug could pass unchanged to systemic blood circulation. An unexpected high dose of the drug in the blood could lead to fatal drug toxicity.
|
|
Most importantly, it performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the longevity of the transplanted organ in the host body (ability to integrate or avoid rejection) and whether it will transform into tumors. Using this method, cells from one mouse could be used to test 1,000 drug compounds to treat liver disease, and reduce animal use by up to 50,000.
|
|
The Nrf2-sMaf heterodimers are critical for oxidative and electrophilic stress response. Nrf2 is known as a master regulator of antioxidant and xenobiotic metabolizing enzyme genes. Induction of these cytoprotective genes is impaired in Nrf2 knockout mice. While MafG, MafK and MafF triple knockout mice die in embryonic stage, cultured cells derived from the triple knockout embryo fail to induce Nrf2-dependent cytoprotective genes in response to stimuli.
|
|
ThOD = (1.5 + 2) mol O2/mol glycine = 3.5 mol O2/mol glycine × 32 g/mol O2 / 75 g/mol glycine = 1.49 g O2/g glycine The theoretical oxygen demand represents the worst-case scenario. The actual oxygen demand of any compound depends on the biodegradability of the compound and the specific organism metabolizing the compound. The actual oxygen demand can be measured experimentally and is called the biochemical oxygen demand (BOD).
|
|
Events that may occur in acute overdose are rare, and include kidney failure and seizure. Susceptible groups of patients, such as children and the elderly, are at greater risk of adverse reactions during therapeutic use. Ofloxacin, like some other fluoroquinolones, may inhibit drug-metabolizing enzymes, and thereby increase blood levels of other drugs such as cyclosporine, theophylline, and warfarin, among others. These increased blood levels may result in a greater risk of side effects.
|
|
The growth and metabolism of these pioneer species changes local environmental conditions (e.g., Eh, pH, coaggregation, and substrate availability), thereby enabling more fastidious organisms to further colonize after them, forming dental plaque. Along with S. sobrinus, S. mutans plays a major role in tooth decay, metabolizing sucrose to lactic acid. The acidic environment created in the mouth by this process is what causes the highly mineralized tooth enamel to be vulnerable to decay.
|
|
The major isolates in lemon verbena oil are citral (30–35%), nerol, and geraniol.Lawless, J., The Illustrated Encyclopedia of Essential Oils, Extracts of lemon verbena also contain verbascoside. As the plant has several phytochemicals which may act as substrates for drug-metabolizing enzymes, lemon verbena may cause herb-drug interactions. However, lemon verbena oil is generally recognized as safe (GRAS) by the US Food and Drug Administration when used as a flavoring.
|
|
Next, the whey must be filtered, and so is loaded into a massive web of ceramic filters and stainless steel turbines. These machines work to separate out the lactose as well as the fats, leaving a liquid of 90% whey protein. Hydrolysates are whey proteins that are predigested and partially hydrolyzed for the purpose of easier metabolizing, but their cost is generally higher. Highly hydrolysed whey may be less allergenic than other forms of whey.
|
|
CYP1A5 and CYP3A37 in turkeys were found to be very similar to the human CYP1A2 and CYP3A4 respectively, in terms of their kinetic properties as well as in the metabolism of aflatoxin B1. CYPs have also been heavily studied in insects, often to understand pesticide resistance. For example, CYP6G1 is linked to insecticide resistance in DDT-resistant Drosophila melanogaster and CYP6M2 in the mosquito malaria vector Anopheles gambiae is capable of directly metabolizing pyrethroids.
|
|
This gene encodes a DNA-dependent adenosine triphosphate (ATP)-metabolizing enzyme that functions as a 5' to 3' DNA helicase. The encoded protein can resolve G-quadruplex structures and RNA-DNA hybrids at the ends of chromosomes. It also prevents telomere elongation by inhibiting the actions of telomerase. Alternative splicing and the use of alternative start codons results in multiple isoforms that are differentially localized to either the mitochondria or the nucleus.
|
|
In a study on men of Japanese ancestry, this has translated to an average increase of total drug exposure by 50–60% compared to men in the United States. However, rabeprazole's metabolism is primarily non-enzymatic (it is often inactivated chemically, without the participation of the body's natural drug metabolizing enzymes). Therefore, while a person's CYP2C19 phenotype will affect rabeprazole's metabolism, it is not expected to dramatically affect the efficacy of the medication.
|
|
Microbiologist Benjamin Elazari Volcani first discovered Haloferax volcanii, a self-named extremophile, in the 1930s. H. volcanii is a halophilic mesophile archaeon that can be isolated from hypersaline environments such as: the Dead Sea, the Great Salt Lake, and oceanic environments with high sodium chloride concentrates. Haloferax volcanii is noteworthy because it can be cultured without much difficulty, rare for an extremophile. H. volcanii is chemoorganotrophic, metabolizing sugars as a carbon source.
|
|
Another observed metabolic phenomenon is the cooperation between Geobacter species, in which several species cooperate in metabolizing a mixture of chemicals that neither could process alone. Provided with ethanol and sodium fumarate, G. metallireducens broke down the ethanol, generating an excess of electrons that were passed to G. sulfurreducens via "nanowires" grown between them, enabling G. sulfurreducens to break down the fumarate ions. The nanowires are made of proteins with metal-like conductivity.
|
|
Since isovaleric acid acid and its esters are natural components of many foods, it is present in mammals including humans. Also, Isovaleryl-coenzyme A is an intermediate in the metabolism of branched- chain amino acids. Isovaleric acid is a major component of the cause of intense foot odor, as it is produced by skin bacteria metabolizing leucine and in rare cases a condition called isovaleric acidemia can lead to heightened levels of this metabolite.
|
|
All asphalt lakes were probably created during the Pleistocene epoch and share the same geological principle. Asphalt lakes are the largest examples of natural oil seeps. They occur when oil migrating toward the surface as a result of buoyancy (oil is lighter than ground water) actually reaches the surface, instead of being trapped in deeper stratigraphic layers. The reason the petroleum becomes asphaltic, or tarry, is the action of oil-metabolizing bacteria.
|
|
The first class of adenylyl cyclases occur in many bacteria including E. coli (as CyaA [unrelated to the Class II enzyme]). This was the first class of AC to be characterized. It was observed that E. coli deprived of glucose produce cAMP that serves as an internal signal to activate expression of genes for importing and metabolizing other sugars. cAMP exerts this effect by binding the transcription factor CRP, also known as CAP.
|
|
Similar to most biomolecules and other orally administered xenobiotics (i.e., drugs), amphetamine is predicted to undergo promiscuous metabolism by human gastrointestinal microbiota (primarily bacteria) prior to absorption into the blood stream. The first amphetamine- metabolizing microbial enzyme, tyramine oxidase from a strain of E. coli commonly found in the human gut, was identified in 2019. This enzyme was found to metabolize amphetamine, tyramine, and phenethylamine with roughly the same binding affinity for all three compounds.
|
|
However, galactose concentration must be fairly high before the enzyme, aldose reductase, will convert significant amounts of the sugar to its galactitol form. As it turns out, the lens is a favorable site for galactose accumulation. The lens phosphorylates galactose at a relatively slow pace in comparison to other tissues. This factor, in combination with the low activity of galactose- metabolizing enzymes in galactosemic patients, allows for the accumulation of galactose in the lens.
|
|
Epoxyeicosatetraenoic acids (EEQs or EpETEs) are a set of biologically active epoxides that various cell types make by metabolizing the omega 3 fatty acid, eicosapentaenoic acid (EPA), with certain cytochrome P450 epoxygenases. These epoxygenases can metabolize EPA to as many as 10 epoxides that differ in the site and/or stereoisomer of the epoxide formed; however, the formed EEQs, while differing in potency, often have similar bioactivities and are commonly considered together.
|
|
Amino acids are released into the blood and converted in the liver to alpha keto acids. Alpha keto acids can then be converted to glucose to maintain proper blood sugar levels. The situation can become dire when one begins to lose muscle mass; this is a sign that the fat has been expended and the body is now metabolizing the muscle tissue. This results in muscle atrophy, a loss of strength and, ultimately, a depletion of muscular tissue completely.
|
|
Cardiac muscle undergoes aerobic respiration patterns, primarily metabolizing lipids and carbohydrates. Oxygen from the lungs attaches to haemoglobin and is also stored in the myoglobin, so that a plentiful supply of oxygen is available. Lipids, and glycogen are also stored within the sarcoplasm and these are broken down by mitochondria to release ATP. The cells undergo twitch-type contractions with long refractory periods followed by brief relaxation periods when the heart fills with blood for the next cycle.
|
|
The pGLO plasmid is an engineered plasmid used in biotechnology as a vector for creating genetically modified organisms. The plasmid contains several reporter genes, most notably the green fluorescent protein (GFP) and the ampicillin resistance gene. GFP was isolated from the jelly fish Aequorea victoria. Because it shares a bidirectional promoter with a gene for metabolizing arabinose, the GFP gene is expressed in the presence of arabinose, which makes the transgenic organism express its fluorescence under UV light.
|
|
Yeast grows exponentially through fermentation of glucose. When glucose levels drop, yeast shift from fermentation to cellular respiration, metabolizing the fermentative products from their exponential growth phase. This shift is known as the diauxic shift after which yeast enter G0. When glucose levels in the surroundings are high, the production of cAMP through the RAS-cAMP-PKA pathway (a cAMP-dependent pathway) is elevated, causing protein kinase A (PKA) to inhibit its downstream target Rim15 and allow cell proliferation.
|
|
Its polysaccharide-metabolizing abilities make it a food source for other components of the microbiome. For example, while B. thetaiotaomicron expresses sialidase enzymes, it cannot catabolize sialic acid; as a result its presence increases the free sialic acid available for other organisms in the gut. These interactions can contribute to the growth of pathogenic bacteria such as Clostridium difficile, which uses sialic acid as a carbon source. Similar interactions can cause B. thetaiotaomicron to exacerbate pathogenic E. coli infection.
|
|
The legislation was introduced in November 2009 as Assembly Bill 556 by Representatives Hebl, Vruwink, Williams, Pasch, Danou, and Fields; it was cosponsored by Senator Taylor. The bill passed the Assembly on May 15, 2010, and was dropped by the Senate on April 28. The use of L. lactis in dairy factories is not without issues. Bacteriophages specific to L. lactis cause significant economic losses each year by preventing the bacteria from fully metabolizing the milk substrate.
|
|
Some anaerobic fermenting microbes in the rumen (and other gastrointestinal tracts) are capable of degrading organic matter to short chain fatty acids, and hydrogen. The accumulating hydrogen inhibits the microbe's ability to continue degrading organic matter, but syntrophic hydrogen-consuming microbes allow continued growth by metabolizing the waste products. In addition, fermentative bacteria gain maximum energy yield when protons are used as electron acceptor with concurrent H2 production. Hydrogen-consuming organisms include methanogens, sulfate-reducers, acetogens, and others.
|
|
As similar promoter methylation pattern, although not yet validated, was also found in human malignant melanoma tissues and human gastric cancer cell lines. These studies allow but certainly do not prove that the silencing of EPHX (i.e. failure to be expressed as ABHD9 protein) is involved in the development and/or progression of certain cancers in humans. More recently, ABHD9 was characterized as possessing epoxy hydrolase activity for metabolizing epoxyeicosatrienoic acids (EETs) and epoxides of linoleic acid (i.e.
|
|
High amount of aerobic glycolysis (also known as the Warburg effect) distinguishes cancer cells from normal cells. The conversion of glucose to lactate rather than metabolizing it in the mitochondria through oxidative phosphorylation, (which can also occur in hypoxic normal cells) persists in malignant tumor despite the presence of oxygen. This process normally inhibits glycolysis which is also known as Pasteur effect. One of the reasons it is observed is because of the malfunction of mitochondria.
|
|
In humans, the CYP2E1 enzyme is encoded by the CYP2E1 gene. The enzyme has been identified in fetal liver, where it is posited to be the predominant ethanol-metabolizing enzyme, and may be connected to ethanol-mediated teratogenesis. In rats, within one day of birth the hepatic CYP2E1 gene is activated transcriptionally. CYP2E1 expression is easily inducible, and can occur in the presence of a number of its substrates, including ethanol, isoniazid, tobacco, isopropanol, benzene, toluene, and acetone.
|
|
Differences in the enzyme occur based on the location of the active site along the amino acid sequence. ACADs are an important class of enzymes in mammalian cells because of their role in metabolizing fatty acids present in ingested food materials. This enzyme's action represents the first step in fatty acid metabolism (the process of breaking long chains of fatty acids into acetyl CoA molecules). Deficiencies in these enzymes are linked to genetic disorders involving fatty acid oxidation (i.e.
|
|
By the time accumulating epigenetic and mutational changes eventually cause hepatocellular carcinoma, epigenetic alterations appear to have an even larger role in carcinogenesis than mutations. Only one gene, TP53, is mutated in more than 20% of liver cancers while 41 genes each have hypermethylated promoters (repressing gene expression) in more than 20% of liver cancers. Alcohol consumption in excess causes a build-up of acetaldehyde. Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage and oxidative stress.
|
|
Drug Metabolism and Disposition is a peer-reviewed scientific journal covering the fields of pharmacology and toxicology. It was established in 1973 and is published monthly by the American Society for Pharmacology and Experimental Therapeutics. The journal publishes articles on in vitro and in vivo studies of the metabolism, transport, and disposition of drugs and environmental chemicals, including the expression of drug-metabolizing enzymes and their regulation. , the editor-in-chief is Edward T. Morgan (Emory University).
|
|
Eoxin A4, also known as 14,15-leukotriene A4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(S)-hydroperoxyeicosapentaenoic acid (i.e. 15(S)-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e.
|
|
Eoxin C4, also known as 14,15-leukotriene C4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(S)-hydroperoxyeicosapentaenoic acid (i.e. 15(S)-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e.
|
|
Eoxin D4, also known as 14,15-leukotriene D4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(S)-hydroperoxyeicosapentaenoic acid (i.e. 15(S)-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e.
|
|
Eoxin E4, also known as 14,15-leukotriene E4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(S)-hydroperoxyeicosapentaenoic acid (i.e. 15(S)-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e.
|
|
The kidney analysis showed that manatees and cormorants had equally high levels. Over all animals, the concentrations were highest in the liver, then kidneys, then lungs, and finally the brain, perhaps indicating a pathway for metabolizing brevetoxin. Dolphins in this study did not show much tissue damage compared to the other two, indicating that brevetoxin has a more profound lethal impact at lower concentrations. Some symptoms of brevetoxicosis on the central nervous system include behavioral changes, muscular impairments, and disorientation.
|
|
The body uses glucose for energy. Without insulin, glucose is unable to enter the cells where it will be used for this and other anabolic ("building up") purposes, such as the synthesis of glycogen, proteins, and fatty acids. (PDF) Insulin is also an active preventor of the breakdown or catabolism of glycogen and fat. The absence of sufficient insulin causes this breaking-down process to be accelerated; it is the mechanism behind metabolizing fat instead of glucose and the appearance of ketones.
|
|
Harvester ants foraging in hot, dry conditions lose water, but obtain water from metabolizing fats in the seeds they eat. Positive feedback on foraging activity, from returning foragers with food, allows the colony to regulate its foraging activity according to the current costs of desiccation and the benefits based on current food availability. In many harvester ant species, foraging behavior is influenced by the weather. For example, in the ant Messor andrei, recruitment to food bait is higher in more humid conditions.
|
|
This lowers the :O2 ratio and therefore also increases photorespiration. and CAM plants have adaptations that allow them to survive in hot and dry areas, and they can therefore out-compete plants in these areas. The isotopic signature of plants shows higher degree of 13C depletion than the plants, due to variation in fractionation of carbon isotopes in oxygenic photosynthesis across plant types. Scientists have designed new metabolism pathways which reduces the losses to photorespiration, by more efficiently metabolizing the toxic glycolate produced.
|
|
When in the bloodstream, more than 99.5% of the substance are bound to plasma proteins. The liver enzyme mainly responsible for metabolizing the drug is CYP3A4; and there are minor contributions from CYP1A2 and CYP2C8. Metabolites identified in tests with human liver cells and microsomes include various hydroxyl derivatives and possibly a carboxylic acid. Only 6% of the circulating substance is in the form of metabolites, and all but one of them are 10- to 20-fold less active than pazopanib itself.
|
|
Acetyl-CoA with the acetyl group indicated in blue. Fats stored in adipose tissue are released from the fat cells into the blood as free fatty acids and glycerol when insulin levels are low and glucagon and epinephrine levels in the blood are high. This occurs between meals, during fasting, starvation and strenuous exercise, when blood glucose levels are likely to fall. Fatty acids are very high energy fuels and are taken up by all metabolizing cells that have mitochondria.
|
|
This is because fatty acids can only be metabolized in the mitochondria.Oxidation of fatty acids Red blood cells do not contain mitochondria and are therefore entirely dependent on anaerobic glycolysis for their energy requirements. In all other tissues, the fatty acids that enter the metabolizing cells are combined with coenzyme A to form acyl-CoA chains. These are transferred into the mitochondria of the cells, where they are broken down into acetyl-CoA units by a sequence of reactions known as β-oxidation.
|
|
Among common E. coli laboratory strains, the 4-HPA degradation pathway is not found in the commonly used K-12 strain, but it does appear in strains B, C, and W (the strain in which most research into the pathway has been done). Only strains containing this pathway are able to survive by metabolizing 4-HPA as the sole carbon source, showing that this pathway is required for catabolism of this compound, and likely for similar phenolic compounds as well.
|
|
5-Hydroxyeicosanoid dehydrogenase (5-HEDH) or more formally, nicotinamide adenine dinucleotide phosphate (NADP+)-dependent dehydrogenase, is an enzyme that metabolizes an eicosanoid product of arachidonate 5-lipoxygenase (5-LOX), 5(S)-hydroxy-6S,8Z,11Z,14Z-eicosatetraenoic acid (i.e. 5-(S)-HETE; see 5-HETE) to its 5-keto analog, 5-oxo-eicosatetraenoic acid (i.e. 5-oxo-6S,8Z,11Z,14Z-eicosatetraenoic acid or 5-oxo-ETE). It also acts in the reverse direction, metabolizing 5-oxo-ETE to 5(S)-HETE.
|
|
The number of bacteria affects the intensity of spoilage, with non-enzymatic Pseudomonas species contributing to spoilage in high number. Food spoilage is detrimental to the food industry due to production of volatile compounds from organisms metabolizing the various nutrients found in the food product. Contamination results in health hazards from toxic compound production as well as unpleasant odours and flavours. Electronic nose technology allows fast and continuous measurement of microbial food spoilage by sensing odours produced by these volatile compounds.
|
|
Cytochrome P450 oxidoreductase deficiency (PORD) is a rare disease and inborn error of metabolism caused by deficiency of cytochrome P450 oxidoreductase (POR). POR is a 2-flavin protein that is responsible for the transfer of electrons from NADPH to all 50 microsomal cytochrome P450 (CYP450) enzymes. This includes the steroidogenic enzymes CYP17A1 (17α-hydroxylase/17,20-lyase), CYP19A1 (aromatase), and CYP21A2 (21-hydroxylase); CYP26B1 (metabolizes retinoic acid); and the hepatic drug-metabolizing CYP450 enzymes (e.g., CYP3A4), among many other CYP450 enzymes.
|
|
When the DNA sequence is altered in genes that regulate cell replication, cancer can result. Mutagenic PAHs, such as benzo[a]pyrene, usually have four or more aromatic rings as well as a "bay region", a structural pocket that increases reactivity of the molecule to the metabolizing enzymes. Mutagenic metabolites of PAHs include diol epoxides, quinones, and radical PAH cations. These metabolites can bind to DNA at specific sites, forming bulky complexes called DNA adducts that can be stable or unstable.
|
|
Samuel Alexander Kinnier Wilson, the neurologist most known for his description of what came to be known as Wilson's disease. Wilson's disease (WD) is a rare inherited disorder in which patients have a problem metabolizing copper. In patients with WD, copper accumulates in the liver and other parts of the body, particularly the brain, eyes and kidneys. Upon accumulation in the brain, patients may experience speech problems, incoordination, swallowing problems, and prominent hyperkinetic symptoms including tremor, dystonia, and gait difficulties.
|
|
The results of the studies at Berkeley and Chicago showed that plutonium's physiological behavior differed significantly from that of radium. The most alarming result was that there was significant deposition of plutonium in the liver and in the "actively metabolizing" portion of bone. Furthermore, the rate of plutonium elimination in the excreta differed between species of animals by as much as a factor of five. Such variation made it extremely difficult to estimate what the rate would be for human beings.
|
|
The first view of the sediment at the bottom of subglacial Lake Whillans, captured by the WISSARD expedition. Image credit: NASA/JPL, California Institute of Technology In subglacial Lake Whillans, the WISSARD expedition collected sediment cores and water samples, which contained 130,000 microbial cells per milliliter and 3,914 different bacterial species. The team identified active bacteria that were metabolizing ammonia, methane, and sulfur from the 120,000-year-old sediments. The most abundant bacteria identified were related to Thiobacillus, Sideroxyans, and pscyhrophilic Polaromonas species.
|
|
Extensions of the adaptive response are the toxic responses elicited by Ahr activation. Toxicity results from two different ways of Ahr signaling. The first is a side effect of the adaptive response in which the induction of metabolizing enzymes results in the production of toxic metabolites. For example, the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), a ligand for Ahr, induces its own metabolism and bioactivation to a toxic metabolite via the induction of CYP1A1 and CYP1B1 in several tissues.
|
|
The olfactory neuroepithelium, which lines the posterior nasal cavity, is exposed to a wide range of odorants and airborne toxic compounds. Odorants, which are mostly small lipophilic molecules, enter the mucus flow and reach the odorant receptors on sensory neurons. Odorant sensing is generally a transient process, requiring an effective signal termination, which could be provided by biotransformation of the odorant in the epithelial supporting cells. Xenobiotic-metabolizing enzymes in the olfactory epithelium have been suggested to catalyze inactivation and facilitate elimination of odorants.
|
|
The olfactory neuroepithelium, which lines the posterior nasal cavity, is exposed to a wide range of odorants and airborne toxic compounds. Odorants, which are mostly small lipophilic molecules, enter the mucus flow and reach the odorant receptors on sensory neurons. Odorant sensing is generally a transient process, requiring an effective signal termination, which could be provided by biotransformation of the odorant in the epithelial supporting cells. Xenobiotic-metabolizing enzymes in the olfactory epithelium have been suggested to catalyze inactivation and facilitate elimination of odorants.
|
|
In the late 1980s R. planticola was genetically modified by inserting a plasmid from Zymomonas mobilis. This plasmid codes for the enzyme pyruvate decarboxylase which, along with alcohol dehydrogenase already present in the bacteria allow it to produce ethanol. The bacteria already does produce ethanol when metabolizing hexoses and pentoses, but very inefficiently. R. planticola was chosen to receive this gene as it already had metabolic pathways to breakdown pentose sugars such as xylose, which is a main component of agricultural and forest residues.
|
|
In molecular biology, the CAT RNA-binding domain (Co-AntiTerminator RNA- binding domain) is a protein domain found at the amino terminus of a family of transcriptional antiterminator proteins. This domain forms a dimer in the crystal structure. Transcriptional antiterminators of the BglG/SacY family are regulatory proteins that mediate the induction of sugar metabolizing operons in Gram-positive and Gram-negative bacteria. Upon activation, these proteins bind to specific targets in nascent mRNAs, thereby preventing abortive dissociation of the RNA polymerase from the DNA template.
|
|
Methods of resistance include thickening of the cuticle of the insect to limit permeation of the insecticide, metabolic resistance via overexpression of metabolizing cytochrome P450 mono-oxygenases and glutathione-S-transferases, and the knockdown resistance (kdr) sodium channel mutations which render the action of insecticides ineffectual, even when co-administered with piperonyl butoxide. Characterization of the different forms of resistance among mosquitoes has become a top priority in groups studying tropical medicine due to the high mortality of those who reside in endemic areas.
|
|
When the cat has no energy from eating, the liver must metabolize fat deposits in the body into usable energy to sustain life. The cat liver, however, is poor at metabolizing fatSarah Wootten DVM, " Why Is My Cat Not Eating?", The Idle Cat, causing a buildup of fat in the cells of the liver, leading to fatty liver. At this point the disease can be diagnosed; however, it will often not be diagnosed, and many animals are euthanized due to improper or no diagnosis.
|
|
Indirubin is a chemical compound most often produced as a byproduct of bacterial metabolism. For instance, it is one of the compounds responsible for the generally benign condition purple urine bag syndrome, resulting from bacteria metabolizing indoxyl sulfate found naturally in urine. Indirubin is a chemical constituent of indigo naturalis (also known as qing dai), which has been used for hundreds of years in traditional Chinese medicine. It is produced by collecting the waste products from the bacterial degradation of specific forms of vegetation.
|
|
Once glycogen is depleted the body begins to fuel the brain using ketones, while also metabolizing body protein (including but not limited to skeletal muscle) to be used to synthesize sugars for use as energy by the rest of the body. Most experts believe that a prolonged fast can lead to muscle wasting, although some dispute this. The use of short-term fasting, or various forms of intermittent fasting, have been used as a form of dieting to circumvent the issues of long fasting.
|
|
For measuring the level of flush reaction to alcohol, the most accurate method is to determine the level of acetaldehyde in the blood stream. This can be measured through both a breathalyzer test or a blood test. Additionally, measuring the amount of alcohol metabolizing enzymes alcohol dehydrogenases and aldehyde dehydrogenase through genetic testing can predict the amount of reaction that one would have. More crude measurements can be made through measuring the amount of redness in the face of an individual after consuming alcohol.
|
|
The rough skinned newt uses a form of chemical based avoidance behavior to avoid being eaten by predators, mainly the common garter snake. The snakes, after swallowing, digesting, and metabolizing a rough-skinned newt, release a chemical signature. This stimulus can be detected by a nearby newt and trigger an avoidant response, which allows them to minimize predation risks. In this way, newts are able to differentiate whether a snake is resistant or sensitive to the toxin in order to avoid being preyed upon.
|
|
Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT eliminates biologically active catechols present in catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When administered with a decarboxylase inhibitor, COMT acts as the major metabolizing enzyme for levodopa and metabolizes it to 3-methoxy-4-hydroxy-L- phenylalanine (3-OMD) in the brain and in the periphery. For the treatment of Parkinson's disease, entacapone is given as an adjunct to levodopa and an aromatic amino acid decarboxylase inhibitor, carbidopa.
|
|
This drug neither inhibits nor unnecessarily induces the action of any major human metabolizing enzymes, which further reduces adverse effects. Early data from phase I trials were optimistic, and found seletracetam to be well tolerated by human volunteers. In phase II trials side effects were limited to the CNS in origin, were of mild to moderate severity, and most were resolved within 24 hours and with no medical intervention. The most frequently reported adverse effects of seletracetam were dizziness, feeling drunk, euphoria, nausea, and somnolence.
|
|
The PLA2G6 gene encodes for a phospholipase A2 enzyme, which is a subclass of enzyme that catalyzes the release of fatty acids from phospholipids. This type of enzyme is responsible for breaking down (metabolizing) phospholipids. Phospholipid metabolism is essential for many body processes, including helping to maintain the integrity of the cell membrane. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.
|
|
Prof. Chakrabarty genetically engineered a new species of Pseudomonas bacteria ("the oil-eating bacteria") in 1971 while working for the Research & Development Center at General Electric Company in Schenectady, New York. At the time, four known species of oil-metabolizing bacteria were known to exist, but when introduced into an oil spill, they competed with each other, limiting the amount of crude oil that they degraded. The genes necessary to degrade oil were carried on plasmids, which could be transferred among species. By irradiating the transformed organism with UV light after plasmid transfer, Prof.
|
|
URB602 ([1,1'-biphenyl]-3-yl-carbamic acid, cyclohexyl ester) is a compound that has been found to inhibit hydrolysis of monoacyl glycerol compounds, such as 2-arachidonoylglycerol (2-AG) and 2-oleoylglycerol (2-OG). It was first described in 2003. A study performed in 2005 found that the compound had specificity for metabolizing 2-AG over anandamide (another cannabinoid ligand) in rat brain presumably by inhibiting the enzyme monoacylglycerol lipase (MAGL), which is the primary metabolic enzyme of 2-AG. However, subsequent studies have shown that URB602 lacks specificity for MAGL inhibition in vitro.
|
|
1.44 Ga stromatolite from Glacier National Park, Montana Prokaryotes were the dominant lifeforms throughout the Boring Billion. Anoxygenic cyanobacteria are thought to have been the dominant photosynthesizers, metabolizing the abundant H2S in the oceans. However, in iron-rich waters, cyanobacteria may have suffered from iron poisoning, especially in offshore waters where iron-rich deep water mixed with surface waters, and were outcompeted by other bacteria which could metabolize both iron and H2S. However, iron poisoning could have been abated by silica-rich waters or biomineralization of iron within the cell.
|
|
In the 1960s it was discovered that when medium-chain triglycerides (MCT) fats are metabolized in the body more ketone bodies are produced then from metabolizing any other fat. Based on this mechanism the MCT ketogenic diet a modification of the ketogenic diet was developed and it has nearly replaced the classic ketogenic diet in the USA. In the MCT ketogenic diet MCT oil is added to ketogenic meals, which allows the carbohydrate content to be increased to around 15 to 20%. This way some patients find the meals more enjoyable.
|
|
Additionally, it should not be taken with dairy products or calcium- fortified juices alone, as peak serum concentration and the area under the serum concentration-time curve can be reduced up to 40%. However, ciprofloxacin may be taken with dairy products or calcium-fortified juices as part of a meal. Ciprofloxacin inhibits the drug-metabolizing enzyme CYP1A2 and thereby can reduce the clearance of drugs metabolized by that enzyme. CYP1A2 substrates that exhibit increased serum levels in ciprofloxacin-treated patients include tizanidine, theophylline, caffeine, methylxanthines, clozapine, olanzapine, and ropinirole.
|
|
Variations in ADME, i.e. an individuals efficiency in absorbing, distributing, metabolizing, and excreting a drug) has been found to occur in cases of the DRESS syndrome, SJS, SJS/TEN, and TEN. These variations influence the levels and duration of a drug or drug metabolite in tissues and thereby impact the drug's or drug metabolite's ability to evoke SCARs. In rare cases, the development of AGEP has been reported to occur in individuals with loss of function mutations in their IL36RN gene. This gene codes for the interleukin 36 receptor antagonist (IL36RA).
|
|
Against other Marvel characters, Cyclops has been able to use his optic beam to knock Thor's Hammer from his hand.Uncanny X-Men #9 He is known to be able to overload Bishop's energy absorption power and is revealed to never have willingly used more than a small fraction of his full potential due to his anxiety regarding his optic blast. Early accounts describe Cyclops' optic beams as the product of his body metabolizing sunlight and other ambient energy.Uncanny X-Men #43 This is similar to his brother Alex (alias Havok) who metabolizes cosmic radiation.
|
|
Individuals are predisposed to develop SCARs in response to a given drug based on the types of human leukocyte antigen (i.e. HLA) proteins and T-cell receptors that they express; their ability to process an instigating drug or the drug's metabolite(s); and other less well-defined factors. These predispositions are a consequence of the HLA allele and T-cell receptor variants that individuals express in their antigen presentation immune pathways; their ADME, i.e. efficiency in Absorbing, Distributing to tissues, Metabolizing, and/or Eliminating a drug or drug metabolite; and other less well-defined factors.
|
|
There are different metabolizing pathways for methacrylonitrile, that are elaborated here: First of all, methacrylonitrile can be directly conjugated with GSH, which leads to the formation of S-(2-cyanopropyl) GSH, which can be metabolized to N-acetyl-S- (2-cyanopropyl) cysteine (NACPC), which can be excreted in the urine. Due to this, glutathione is depleted to certain degrees after MeAN exposure. After oral exposure to 100 mg/kg MeAN in rats, the maximum depletion was noticed in the liver at 39% of control. This depletion, however, is less than found after AN administration.
|
|
One of the mechanisms of antineoplastic resistance is over-expression of drug-metabolizing enzymes or carrier molecules. By increasing expression of metabolic enzymes, drugs are more rapidly converted to drug conjugates or inactive forms that can then be excreted. For example, increased expression of glutathione promotes drug resistance, as the electrophilic properties of glutathione allow it to react with cytotoxic agents, inactivating them. In some cases, decreased expression or loss of expression of drug-metabolising enzymes confers resistance, as the enzymes are needed to process a drug from an inactive form to an active form.
|
|
It has been proposed that modification of gene expression from nongenotoxic carcinogens can occur by oxidative stress, peroxisome proliferation, suppression of apoptosis, alteration of intercellular communication, and modulation of metabolizing enzymes. Carbon tetrachloride is an example of a probable nongenotoxic carcinogen to aquatic vertebrates. Historically, carbon tetrachloride has been used in pharmaceutical production, petroleum refining, and as an industrial solvent.National Toxicology Program, 2011 Due to its widespread industrial use and release into the environment, carbon tetrachloride has been found in drinking water and therefore, has become a concern for aquatic organisms.
|
|
EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases, particularly soluble epoxide hydrolase, and therefore act locally. CYP4F8 has little activity in omega-hydroxylating leukotriene B4, prostaglandin D2, prostaglandin E2, prostaglandin E1, or prostaglandin F2. The fatty acid metabolizing activity, including the ability to form epoxides, of CYP4F8 is very similar to that of CYP4F12. However, it and CYP4F12 are not regarded as being major contributors in forming the cited epoxides in humans although they might do so in tissues where they are highly expressed.
|
|
B. thetaiotaomicron is capable of metabolizing a very diverse range of polysaccharides. Its complement of enzymes for hydrolysis of glycosidic bonds is among the largest known in prokaryotes, and it is thought to be capable of hydrolyzing most glycosidic bonds in biological polysaccharides. As a component of the human gut flora, it can use both dietary carbohydrates and those sourced from the host, depending on nutrient availability. Although it is considered an obligate anaerobe, B. thetaiotaomicron is aerotolerant and can survive, but not grow, when exposed to oxygen.
|
|
However, maximum productivity is limited due to the fact that these organisms cannot use pentose sugars, leading to consideration of E.coli and Clostridia. E.coli is capable of producing ethanol under anaerobic conditions through metabolizing glucose into two moles of formate, two moles of acetate, and one mole of ethanol. While bioethanol has proved to be a successful alternative fuel source on an industrial scale, it also has its shortcomings, namely, its low energy density, high vapor pressure, and hygroscopicity. Current alternatives to bioethanol include biobutanol, biodiesel, propanol, and synthetic hydrocarbons.
|
|
Certain approaches in alternative medicine claim to remove "toxins" from the body through herbal, electrical or electromagnetic treatments. These toxins are undefined and have no scientific basis, making the validity of such techniques questionable. There is little evidence for toxic accumulation in these cases, as the liver and kidneys automatically detoxify and excrete many toxic materials including metabolic wastes. Under this theory if toxins are too rapidly released without being safely eliminated (such as when metabolizing fat that stores toxins) they can damage the body and cause malaise.
|
|
Cholesterol-24 hydroxylase contributes to brain cholesterol homeostasis by hydroxylating cholesterol at carbon-24 to 24S-hydroxycholesterol to allow for elimination of cholesterol from the brain to the liver. Only around 6–7 mg of cholesterol, however, are hydroxylated by this enzyme on a daily basis, suggesting the existence of alternative functions – presently unknown. In vitro experiments have shown that it is also capable of further metabolizing 24S-hydroxycholesterol into 24,25- and 24,27-dihydroxycholesterols. Cholesterol-24 hydroxylase has a variety of possible substrates, including: elongated steroid chains, cholesterol derivatives, and a variety of drug candidates.
|
|
By the 1970s, other researchers and hospitals had begun to use lipoic acid for the treatment of chronic liver disease. It has since been used experimentally to treat pancreatic cancer and its use as a dietary supplement to prevent or delay the onset of Alzheimer's disease and Parkinson's disease has been proposed. During the 1960s and 1970s, Gunsalus studied Cytochrome P450, researching its role in metabolism in the human liver. His studies led to an understanding of how the family of P-450 proteins and their role in metabolizing natural and man-made compounds.
|
|
Synthetically produced ammonia and nitrates are key industrial fertilisers, and fertiliser nitrates are key pollutants in the eutrophication of water systems. Apart from its use in fertilisers and energy-stores, nitrogen is a constituent of organic compounds as diverse as Kevlar used in high-strength fabric and cyanoacrylate used in superglue. Nitrogen is a constituent of every major pharmacological drug class, including antibiotics. Many drugs are mimics or prodrugs of natural nitrogen-containing signal molecules: for example, the organic nitrates nitroglycerin and nitroprusside control blood pressure by metabolizing into nitric oxide.
|
|
Ravindranath earned her B.Sc. and M.Sc. degrees from Andhra University and received her Ph.D. (Biochemistry) in 1981 from Mysore University and worked at the National Cancer Institute, USA as a Postdoctoral Fellow. She joined the National Institute of Mental Health and Neurosciences, Bangalore, where she studied the metabolizing capacity of the human brain, focusing especially on psychoactive drugs and environmental toxins. In 1999, she helped Department of Biotechnology (DBT), Government of India to establish National Brain Research Centre (NBRC), an autonomous institution of DBT to co-ordinate and network neuroscience research groups in India.
|
|
The effects last because grapefruit-mediated inhibition of drug metabolizing enzymes, like CYP3A4, is irreversible; that is, once the grapefruit has "broken" the enzyme, the intestinal cells must produce more of the enzyme to restore their capacity to metabolize drugs that the enzyme is used to metabolize. It takes around 24 hours to regain 50% of the cell's baseline enzyme activity and it can take 72 hours for the enzyme activity to completely return to baseline. For this reason, simply separating citrus consumption and medications taken daily does not avoid the drug interaction.
|
|
20alpha-HSD has been initially described as a progesterone metabolizing enzyme of the ovary. On a functional level, ovarian 20alpha-HSD is actively involved in the control of progesterone homeostasis in pregnancy of rats and mice. While 20alpha-HSD expression and activity is downregulated in the corpus luteum of pregnancy, 24 hrs prior to parturition ovarian 20alpha-HSD activity is acutely stimulated. Accordingly, in mice with targeted deletion of the 20alpha-HSD gene, progesterone blood concentration remain high throughout pregnancy which results in a delay of 2–4 days in parturition.
|
|
Galactosemia is one of the most mysterious of the heavily- researched metabolic diseases. It is a hereditary disease that results in a defect in, or absence of, galactose-metabolizing enzymes. This inborn error leaves the body unable to metabolize galactose, allowing toxic levels of galactose to build up in human body blood, cells, and tissues. Although treatment for galactosemic infants is a strict galactose-free diet, endogenous (internal) production of galactose can cause symptoms such as long-term morbidity, presenile development of cataract, renal failure, cirrhosis, and cognitive, neurologic, and female reproductive complications.
|
|
The substrate specificity of 5-HEDH has been evaluated in a variety of intact cells and in crude microsome preparations isolated from cultured human blood monocytes differentiated into macrophages. These studies indicate that the enzyme efficiently oxidizes long chain unsaturated fatty acids possessing a hydroxy residue at carbon 5 and a trans double bound at carbon 6 to their corresponding 5-oxo products. It is therefore most efficient in metabolizing 5(S)-HETE to 5-oxo-ETE and, with somewhat lesser efficiency, in metabolizing other 5(S)-hydroxyl-6-trans unsaturated fatty acids such as 5(S)-hydroxy- eicosapentaenoic acid, 5(S)-hydroxy-eicosatrienoic acid, 5(S)-hydroxy- eicosadeinoic acid, 5(S)-hydroxy-eicosamonoenoic acid, 5(S)-hydroxy- octadecadienoic acid, 5(S),15(S)-dihydroxyeicosatetraenoic acid, and the 6-trans isomer of leukotriene B4 (which is a 5(S),12(S)-dihydroxyeicosatetraeonic acid) to their corresponding oxo analogs. 5-HEDH has relatively little ability to oxidize 5(S)-hydroxyl-tetradecadienoic acid, the R stereoisomer of 5(S)-HETE (5(R)-HETE), or a racemic mixture of 8-HETE, and does not oxidize 12(S)-HETE, 15(S)-HETE, leukotriene B4, a racemate mixture of 9-HETE, a racemate mixture of 11-HETE, or a 5(S)-hydroxy-6-trans 12 carbon dienoic fatty acid.
|
|
Mitochondria of a mammal lung cell visualized using Transmission Electron Microscopy Mitochondria are organelles that synthesize ATP for the cell by metabolizing carbon-based macromolecules. The presence of deoxyribonucleic acid (DNA) in mitochondria and proteins, derived from mtDNA, suggest that this organelle may have been a prokaryote prior to its integration into the proto-eukaryote. Mitochondria are regarded as organelles rather than endosymbionts because mitochondria and the host cells share some parts of their genome, undergo mitosis simultaneously, and provide each other means to produce energy. Endomembrane system and nuclear membrane were hypothesized to have derived from the protomitochondria.
|
|
With an exercise intensity higher than the threshold the lactate production exceeds the rate at which it can be broken down. The blood lactate concentration will show an increase equal to 4.0mM; it then accumulates in the muscle and then moves to the bloodstream. Regular endurance exercise leads to adaptations in skeletal muscle which raises the threshold at which lactate levels will rise. This is mediated via activation of PGC-1α, which alters the isoenzyme composition of the LDH complex and decreases the activity of the lactate generating enzyme LDHA, while increasing the activity of the lactate metabolizing enzyme LDHB.
|
|
ODD also tends to occur in families with a history of ADHD, substance use disorders, or mood disorders, suggesting that a vulnerability to develop ODD may be inherited. A difficult temperament, impulsivity, and a tendency to seek rewards can also increase the risk of developing ODD. New studies into gene variants have also identified possible gene-environment (G x E) interactions, specifically in the development of conduct problems. A variant of the gene that encodes the neurotransmitter metabolizing enzyme mono amine oxidase-A (MAOA), which relates to neural systems involved in aggression, plays a key role in regulating behavior following threatening events.
|
|
Atheroma) plaques as well as inflamed tonsils. CYP2S1 is expressed in macrophages, liver, lung, intestine, and spleen; is abundant in human and mouse atherosclerosis (i.e. Atheroma) plaques as well as inflamed tonsils; and, in addition to forming epoxides of arachidonic acid (and other polyunsaturated fatty acids), CYP2S1 metabolizes prostaglandin G2 and Prostaglandin H2 to 12-Hydroxyheptadecatrienoic acid. Possibly because of metabolizing and thereby inactivating the prostaglandins and/or because forming the bioactive metabolite, 12-hyddroxyheptadecatrienoic acid, rather than EETs, CYP2S1 may act to inhibit the function of monocytes and thereby limit inflammation as well as other immune responses.
|
|
RDH13 is part of a subfamily of four retinol dehydrogenases, RDH11, RDH12, RDH13, and RDH14, that display dual-substrate specificity, uniquely metabolizing all- trans- and cis-retinols with C(15) pro-R specificity. The metabolites involved in these reactions are known as retinoids, which are chromophores involved in vision, transcriptional regulation, and cellular differentiation. RDH11-14 could be involved in the first step of all-trans- and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor and retinal pigment epithelial cells.
|
|
In the 1960s, Curtis Dohan speculated that the low incidence of schizophrenia in certain South Pacific Island societies was a result of a diet low in wheat and milk-based foods. Dohan proposed a genetic defect wherein individuals are incapable of completely metabolizing gluten and casein as a possible cause for schizophrenia. Dohan hypothesized that elevated peptide levels from this incomplete metabolism could be responsible for schizophrenic behaviors. In 1979, Jaak Panksepp proposed a connection between autism and opiates, noting that injections of minute quantities of opiates in young laboratory animals induce symptoms similar to those observed among autistic children.
|
|
Two pathophysiologic mechanisms are thought to play a role in the development of gray baby syndrome after exposure to the anti-microbial drug chloramphenicol. This condition is due to a lack of glucuronidation reactions occurring in the baby, thus leading to an accumulation of toxic chloramphenicol metabolites: # The UDP-glucuronyl transferase enzyme system of infants, especially premature infants, is immature and incapable of metabolizing the excessive drug load. # Insufficient renal excretion of the unconjugated drug. Insufficient metabolism and excretion of chloramphenicol leads to increased blood concentrations of the drug, causing blockade of the electron transport of the liver, myocardium, and skeletal muscles.
|
|
In termites, the endosymbionts reside within the hindguts and are transmitted through trophallaxis among colony members. The primary endosymbionts are thought to help the host either by providing nutrients that the host cannot obtain itself or by metabolizing insect waste products into safer forms. For example, the putative primary role of Buchnera is to synthesize essential amino acids that the aphid cannot acquire from its natural diet of plant sap. Likewise, the primary role of Wigglesworthia, it is presumed, is to synthesize vitamins that the tsetse fly does not get from the blood that it eats.
|
|
Triosephosphate isomerase (TPI) is a central enzyme of glycolysis, the main pathway for cells to obtain energy by metabolizing sugars. In humans, certain mutations within this enzyme, which affect the dimerisation of this protein, are causal for a rare disease, triosephosphate isomerase deficiency. Other mutations, which inactivate the enzyme (= null alleles) are lethal when inherited homozygously (two defective copies of the TPI gene), but have no obvious effect in heterozygotes (one defective and one normal copy). However, the frequency of heterozygous null alleles is much higher than expected, indicating a heterozygous advantage for TPI null alleles.
|
|
It has been speculated that atmospheric static electricity may have played a role in the inconclusive results from the Viking lander life experiments, which were positive for metabolizing microbial life, but no organic compounds were detected by the mass spectrometer. The two favored possible explanations are reactions with hydrogen peroxide or ozone created by ultraviolet light or atmospheric electrical processes during dust storms. DREAMS-P was a pressure sensor and DREAMS-H was for humidity;the sensors feed a single data-handling circuit board. In addition to the surface payload, a camera called DECA (Descent Camera) on the lander operated during the descent.
|
|
In addition, ethanol metabolism follows first-order kinetics at very high concentrations, with an elimination half-life of about 4 or 4.5 hours (which implies a clearance rate of approximately 6 L/hour/70 kg). This seems to be because other processes, such as the MEOS/CYP2E1, also become involved in the metabolism of ethanol at higher concentrations. However, the MEOS/CYP2E1 alone does not appear sufficient to fully explain the increase in ethanol metabolism rate. Some individuals have less effective forms of one or both of the metabolizing enzymes of ethanol, and can experience more marked symptoms from ethanol consumption than others.
|
|
CYP2C19 is an important drug- metabolizing enzyme that catalyzes the biotransformation of many clinically useful drugs, including antidepressants, barbiturates, proton-pump inhibitors, and antimalarial and antitumor drugs. Clopidogrel is one of the drugs metabolized by this enzyme. Several landmark studies have proven the importance of 2C19 genotyping in treatment using clopidogrel. In March 2010, the U.S. Food and Drug Administration (FDA) put a black box warning on Plavix to make patients and healthcare providers aware that CYP2C19-poor metabolizers, representing up to 14% of patients, are at high risk of treatment failure and that testing is available.
|
|
Urodilatin is little affected by renal enzymes that inactivate atriopeptin, as the kidney elutes with urodilatin rather than with ANP. The degradation rates of (125I)-urodilatin and [125I]-ANP by pure recombinant NEP (rNEP) were compared. Phosphoramidon, a potent inhibitor of NEP, completely protected both peptides from metabolism by rNEP. Urodilatin has a four-residue extension at the N-terminus neutral endopeptidase-24.11 (NEP) plays a physiological role in metabolizing atrial natriuretic peptide, and C-type natriuretic peptide (prohormone) degraded the bioactive peptides at about half the rate though the C-terminal that compete with natriuretic peptides for hydrolysis by neutral endopeptidase.
|
|
A number of molecular genetics studies have focused on manipulating candidate aggression genes in mice and other animals to induce effects that can be possibly applied to humans. Most studies have focused on polymorphisms of serotonin receptors, dopamine receptors, and neurotransmitter metabolizing enzymes. Results of these studies have led to linkage analysis to map the serotonin-related genes and impulsive aggression, as well as dopamin-related genes and proactive aggression. In particular, the serotonin 5-HT seems to be an influence in inter-male aggression either directly or through other molecules that use the 5-HT pathway.
|
|
By providing both food and microhabitats for many species, coarse woody debris helps to maintain the biodiversity of forest ecosystems. Up to forty percent of all forest fauna is dependent on CWD. Studies in western North America showed that only five per cent of living trees consisted of living cells by volume, whereas in dead wood it was as high as forty percent by volume, mainly fungi and bacteria. Colonizing organisms that live on the remains of cambium and sapwood of dead trees aid decomposition and attract predators that prey on them and so continue the chain of metabolizing the biomass.
|
|
Geniposide has been reported as having a hypoglycemic effect, which could be mediated by hepatic glucose- metabolizing enzymes, such as hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase). GP and G6Pase are induced by chronic hyperglycemia. High levels of blood sugar increased their expression and activity, which lead to an increase in hepatic glucose production and unbalance the glucose metabolism. A study with the high-fat diet (HFD) - streptozotocin (STZ) diabetic mouse model using geniposides doses of 200 and 400 (mg/kg) has shown a significant decrease in body weight, blood glucose, insulin and triglycerides (TG) levels.
|
|
Hemolytic anemia due to G6PD deficiency following Fava beans consumption Glucose-6-phosphate dehydrogenase (G6PD) is an important enzyme in red cells, metabolizing glucose through the pentose phosphate pathway, an anabolic alternative to catabolic oxidation (glycolysis), while maintaining a reducing environment. G6PD is present in all human cells but is particularly important to red blood cells. Since mature red blood cells lack nuclei and cytoplasmic RNA, they cannot synthesize new enzyme molecules to replace genetically abnormal or ageing ones. All proteins, including enzymes, have to last for the entire lifetime of the red blood cell, which is normally 120 days.
|
|
The PTGS (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins in two steps. First, hydrogen is abstracted from carbon 13 of arachidonic acid, and then two molecules of oxygen are added by the PTGS2 (COX-2), giving PGG2. Second, PGG2 is reduced to PGH2 in the peroxidase active site. The synthesized PGH2 is converted to prostaglandins (PGD2, PGE2, PGF2α), prostacyclin (PGI2), or thromboxane A2 by tissue-specific isomerases.(Figure 2) While metabolizing arachidonic acid primarily to PGG2, COX-2 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids (i.e.
|
|
For instance, Tamoxifen used to be a drug commonly prescribed to women with ER+ breast cancer, but 65% of women initially taking it developed resistance. After some research by people such as David Flockhart, it was discovered that women with certain mutation in their CYP2D6 gene, a gene that encodes the metabolizing enzyme, were not able to efficiently break down Tamoxifen, making it an ineffective treatment for their cancer. Since then, women are now genotyped for those specific mutations, so that immediately these women can have the most effective treatment therapy. Screening for these mutations is carried out via high- throughput screening or phenotypic screening.
|
|
Like allolactose, IPTG binds to the lac repressor and releases the tetrameric repressor from the lac operator in an allosteric manner, thereby allowing the transcription of genes in the lac operon, such as the gene coding for beta-galactosidase, a hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides. But unlike allolactose, the sulfur (S) atom creates a chemical bond which is non-hydrolyzable by the cell, preventing the cell from metabolizing or degrading the inducer. Therefore, its concentration remains constant during an experiment. IPTG uptake by E. coli can be independent of the action of lactose permease, since other transport pathways are also involved.
|
|
Enoyl-CoA hydratase (ECH) or crotonase is an enzyme that hydrates the double bond between the second and third carbons on 2-trans/cis-enoyl-CoA: 460x460px File:Enoyl-CoA hydratase reaction cis.svg ECH is essential to metabolizing fatty acids in beta oxidation to produce both acetyl CoA and energy in the form of ATP. ECH of rats is a hexameric protein (this trait is not universal, but human enzyme is also hexameric), which leads to the efficiency of this enzyme as it has 6 active sites. This enzyme has been discovered to be highly efficient, and allows people to metabolize fatty acids into energy very quickly.
|
|
Sequences have been found in other organisms that encode gene products with a similar function to dnaQ: In Mycobaterium tuberculosis, the gene dnaE1 encodes a polymerase and histidinol-phosphatase (PHP) domain that carries out the 3’→5’ exonuclease and proofreading function. TREX1, the major 3'→5' exonuclease in humans, was initially called DNase III because it showed sequence homology with dnaQ in E. coli and with eukaryotic DNA polymerase epsilon and to possess biochemical characteristics that associate with the capability of DNA proofreading. It is responsible for metabolizing both single stranded DNA (ssDNA) and double stranded DNA (dsDNA) with mismatched 3' ends and is directed by endogenous retroelements.
|
|
Oxcarbazepine is a structural derivative of carbamazepine, with a ketone in place of the carbon–carbon double bond on the dibenzazepine ring at the 10 position (10-keto). This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia or agranulocytosis occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine — sodium channel inhibition (presumed to be the main mechanism of action) – and is generally used to treat the same conditions. Oxcarbazepine is a prodrug which is activated to licarbazepine in the liver.
|
|
When Havok strikes an object with hot plasma, the sudden temperature jump often causes objects to shatter or disintegrate. Should Havok direct his energy at the lowest level, he can project it towards a human being and his target will suffer a severe headache, but will not burn up. He can absorb cosmic energy from his environment (such as starlight, x-rays, and gamma radiation) and store them in his cells, metabolizing the energy to generate plasma wave discharges that super-heat and disintegrate objects. His absorption is normally passive, but he has shown that he can actively drain and absorb energy as well.
|
|
In mice, the only 20-HETE- and 19-HETE-producing enzymes of the Cyp4a subfamily are two extensively homologous ones, Cyp4a12a and Cyp4a12b; Cyp4a12a is expressed in the male kidney in an androgen hormone- dependent manner. In rats, Cyp4a1, Cyp4a2, Cyp4a3, and Cyp4a8 make 20-HETE. The tissue distribution of these enzymes differs from those of humans making extrapolations from rodent studies to humans somewhat complicated. Mouse CYP2J9, rat CYP2J3, and sheep CYP2J metabolize arachidonic acid primarily to 19-HETE but also to smaller amounts of 20-HETE, and, in the case of the sheep enzyme, 18-HETE; human CYP2J2, however, is an epoxygenase, metabolizing arachidonic acid to epoxide products.
|
|
In contrast, conversion of the hydrogen at the C5 site from the α → β configuration reflects anaerobic microbial activity, and can be understood through isotope labeling experiments on controlled microbe experiments metabolizing the steroid of interest. One study demonstrated that there are two reactions that can produce loss of the cholesterol double bond—(1) direct reduction of double bond or (2) production of ketone prior to reduction of double bond—resulting in distinct isomerization of the hydrogen at the C5 site. The 14 and 17α hydrogen sites are more stable and undergo changes to β configuration in much lower abundances than the 5 hydrogen site.
|
|
The gas exchange (GEX) experiment (PI: Vance Oyama, NASA Ames) looked for gases given off by an incubated soil sample by first replacing the Martian atmosphere with the inert gas helium. It applied a liquid complex of organic and inorganic nutrients and supplements to a soil sample, first with just nutrients added, then with water added too. Periodically, the instrument sampled the atmosphere of the incubation chamber and used a gas chromatograph to measure the concentrations of several gases, including oxygen, CO2, nitrogen, hydrogen, and methane. The scientists hypothesized that metabolizing organisms would either consume or release at least one of the gases being measured.
|
|
Biomachining is the machining process of using lithotropic bacteria to remove material from metal parts, contrasted with chemical machining methods such as chemical milling and physical machining methods such as milling. Certain bacteria, such as Thiobacillus ferrooxidans and Thiobacillus thiooxidans, which are also used in the mineral refinement process of bioleaching, utilize the chemical energy from oxidation of iron or copper to fix carbon dioxide from the air. A metal object, when placed in a culture fluid containing these metal-metabolizing bacteria, will have material removed from its surface over time. Biomachining is ideal for micromachining due to its very low material removal rate.
|
|
This aspect was studied in Porto as well. Metabolizing enzymes, namely monoamine oxidase und catechol-O-methyl transferase (COMT), as well as carrier proteins for the transport through cell membranes contributed to the removal of catecholamines from the extracellular space, thus from the neighbourhood of the receptors, and hence to loss of effect. The role played by these processes differed between the various catecholamines and the various tissues. One pervading difference was that inhibitors of COMT enhanced the effect of isoprenaline at β-adrenoceptors (and the ensuing blood vessel relaxation) but not the effect of noradrenaline at α-adrenoceptors (and the ensuing blood vessel contraction).
|
|
He also has Case's pancreas replaced and new tissue grafted into his liver, leaving Case incapable of metabolizing cocaine or amphetamines and apparently ending his drug addiction. Cover of a Brazilian edition, depicting the character of "razorgirl" Molly Millions Case develops a close personal relationship with Molly, who suggests that he begin looking into Armitage's background. Meanwhile, Armitage assigns them their first job: they must steal a ROM module that contains the saved consciousness of one of Case's mentors, legendary cyber-cowboy McCoy Pauley, nicknamed "Dixie Flatline." Armitage needs Pauley's hacking expertise, and the ROM construct is stored in the corporate headquarters of media conglomerate Sense/Net.
|
|
Entacapone, sold under the brand name Comtan among others, is a medication commonly used in combination with other medications for the treatment of Parkinson's disease. Entacapone together with levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson's disease signs and symptoms for a greater length of time than levodopa and carbidopa therapy alone. Entacapone is a selective and reversible inhibitor of the enzyme catechol-O-methyltransferase (COMT). When taken together with levodopa (L-DOPA) and carbidopa, entacapone stops catechol-O-methyltransferase from breaking down and metabolizing levodopa, resulting in an overall increase of levodopa remaining in the brain and body.
|
|
In the treatment of epilepsy, drugs such as vigabatrin that target both GABA transporters and the GABA metabolizing enzyme GABA-transaminase have been marketed, providing proof of principle for the neurotransmitter cycling systems as pharmacological targets. However, with regard to glutamate transport and metabolism, no such drugs have been developed, because glutamatergic synapses are abundant, and the neurotransmitter glutamate is an important metabolite in metabolism, making interference capable of adverse effects. So far, most of the drug development directed at the glutamatergic system seems to have been focused on ionotropic glutamate receptors as pharmacological targets, although G-protein coupled receptors have been attracting increased attention over the years.
|
|
Eoxins are proposed to be a family of proinflammatory eicosanoids (signaling compounds that regulate inflammatory and immune responses). They are produced by human eosinophils (a class of white blood cells), mast cells, the L1236 Reed–Sternberg cell line derived from Hodgkin's lymphoma, and certain other tissues. These cells produce the eoxins by initially metabolizing arachidonic acid, an omega-6 (ω-6) fatty acid, via any enzyme possessing 15-lipoxygenase activity. The product of this initial metabolic step, 15(S)-hydroperoxyeicosatetraenoic acid, is then converted to a series of eoxins by the same enzymes that metabolize the 5-lipoxygenase product of arachidonic acid metabolism, i.e.
|
|
Some of the substances inhaled from using these products are carcinogens. The physiological changes, such as inflammation in multiple organ systems, energy metabolism, and carcinogenesis, in response to heated tobacco emissions, has not been well characterized due to limited research in this area, especially in animal models. A 2018 in vitro study suggested a less harmful pathophysiological response in human organotypic oral epithelial cultures when exposed to such emissions. A 2016 animal study showed that heated tobacco emissions did not increase surfactant lipids, surfactant proteins, surfactant metabolizing proteins, inflammatory eicosanoids, and their metabolic enzymes, and several ceramide classes, compared with tobacco cigarette smoke-exposed mice.
|
|
A number of foods and substances have been found to disturb sleep, due to stimulant effects or disruptive digestive demands. Avoiding nicotine, caffeine (including coffee, energy drinks, soft drinks, tea, chocolate, and some pain relievers), and other stimulants in the hours before bedtime is recommended by most sleep hygiene specialists, as these substances activate neurobiological systems that maintain wakefulness. Alcohol near bedtime is frequently discouraged by clinicians, because, although alcohol can induce sleepiness initially, the arousal caused by metabolizing alcohol can disrupt and significantly fragment sleep. Smoking tobacco products before bed is also thought to reduce one's quality of resting by decreasing the time spent in deep sleep, leading to sleep fragmentation and nocturnal restlessness.
|
|
The relationship between some gut flora and humans is not merely commensal (a non-harmful coexistence), but rather a mutualistic relationship. Some human gut microorganisms benefit the host by fermenting dietary fiber into short-chain fatty acids (SCFAs), such as acetic acid and butyric acid, which are then absorbed by the host. Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics. The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ, and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.
|
|
Grapefruit and grapefruit juice have been found to interact with numerous drugs and in many cases, to result in adverse direct and/or side effects (if dosage is not carefully adjusted.) This happens in two very different ways. In the first, the effect is from bergamottin, a natural furanocoumarin in both grapefruit flesh and peel that inhibits the CYP3A4 enzyme (among others from the P450 enzyme family responsible for metabolizing 90% of drugs). The action of the CYP3A4 enzyme itself is to metabolize many medications. If the drug's breakdown for removal is lessened, then the level of the drug in the blood may become too high or stay too long, leading to adverse effects.
|
|
In addition to being an addictive substance, it has also been shown to lead to adverse health effects, such as irregular sleeping patterns, increase in blood pressure, palpitations, and anxiety. Decaffeination has been traditionally recommended to reduce caffeine content in food and beverages, but to perform decaffeination by physio-chemical treatments is expensive and can produce other waste that may require further treatment. Thus, microbial bioprocessing has begun to appear more attractive, with bacteria that are capable of metabolizing caffeine being considered. Specifically, bacteria containing caffeine dehydrogenase have been seen as helpful in treating caffeine in agro-industrial wastes of coffee pulps and husks, which can then be used to feed farm animals.
|
|
Under the microscope, Pediococcus often appear in pairs of pairs or tetrads which can make them identifiable. Pediococci are homofermenters, metabolizing glucose into a racemic mixture of both L- and D-lactate by glycolysis. However, in the absence of glucose, some species, such as P. pentosaceus, begin using glycerol, degrading it into pyruvate which later can be converted to diacetyl, acetate, 2,3-butanediol and other compounds that can impart unfavorable characteristics to the wine. Most Pediococcus species are undesirable in winemaking due to the high levels of diacetyl that can be produced, as well as increased production of biogenic amines that has been implicated as one potential cause for red wine headaches.
|
|
Additionally, the rough surface of rusty metal provides crevices for dirt containing C. tetani, while a nail affords a means to puncture skin and deliver endospores deep within the body at the site of the wound. An endospore is a non-metabolizing survival structure that begins to metabolize and cause infection once in an adequate environment. Hence, stepping on a nail (rusty or not) may result in a tetanus infection, as the low-oxygen (anaerobic) environment may exist under the skin, and the puncturing object can deliver endospores to a suitable environment for growth. It is a common misconception that rust itself is the cause and that a puncture from a rust-free nail is not a risk.
|
|
Esmolol is considered a soft drug, one that is rapidly metabolized to an inactive form. Esmolol is rapidly metabolized by hydrolysis of the ester linkage, chiefly by the esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase. Total body clearance in man was found to be about 20 L/kg/hr, which is greater than cardiac output; thus the metabolism of esmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flow. Esmolol's short duration of action is based on the ester-methyl side chain which allows for quick hydrolysis.
|
|
The development of the Human Epigenome Project and advances in epigenomics has given rise to a burgeoning field known as pharmacoepigenetics. Pharmacoepigenetics was initially developed to study how epigenetic patterns of drug transporters, drug-metabolizing enzymes, and nuclear receptors affect individuals’ response to the drug. Now, pharmacoepigenetics has an additional focus: the development of therapeutic epidrugs that can make changes to the epigenome in order to lessen the cause or symptoms of a disease in an individual. Even though a large gap still remains between the knowledge of epigenetic modifications on drug metabolism mechanisms and clinical applications, pharmacoepigenetics has become a rapidly growing field that has the potential to play an important role in personalized medicine.
|
|
A polymorphic variant of a gene can lead to the abnormal expression or to the production of an abnormal form of the protein; this abnormality may cause or be associated with disease. For example, a polymorphic variant of the gene encoding the enzyme CYP4A11, in which thymidine replaces cytosine at the gene's nucleotide 8590 position encodes a CYP4A11 protein that substitutes phenylalanine with serine at the protein's amino acid position 434. This variant protein has reduced enzyme activity in metabolizing arachidonic acid to the blood pressure-regulating eicosanoid, 20-Hydroxyeicosatetraenoic acid. A study has shown that humans bearing this variant in one or both of their CYP4A11 genes have an increased incidence of hypertension, ischemic stroke, and coronary artery disease.
|
|
Diagram of how euxinic conditions form In 1998, geologist Donald Canfield proposed what is now known as the Canfield ocean hypothesis. Canfield claimed that increasing levels of oxygen in the atmosphere at the Great Oxygenation Event would have reacted with and oxidized continental iron pyrite (FeS2) deposits, with sulfate (SO42−) as a byproduct, which was transported into the sea. Sulfate-reducing microorganisms converted this to hydrogen sulfide (H2S), dividing the ocean into a somewhat oxic surface layer, and a sulfidic layer beneath, with anoxygenic bacteria living at the border, metabolizing the H2S and creating sulfur as a waste product. This created widespread euxinic conditions in middle-waters, an anoxic state with a high sulfur concentration, which was maintained by the bacteria.
|
|
Compared to CAOV-3 human ovarian cancer cells, SKOV-3 and CAOV-3 human ovarian cancer cells over express BLT4 receptors, LTB4 and 12-HETE metabolizing enzymes, two key metabolites of these enzymes, LTB4 and 12-HETE, and activated STAT3 also are far more invasive in animal models. Inhibition of BLT2 receptors by LY255283 but not of BLT1 receptors by U75302 and suppression of BLT2 receptors by siRNA treatment reduced the expression of NOX4 (i.e. NADPH oxidase 4, the reactive oxygen species made by this enzyme, activated STAT3, the invasion- promoting enzyme, MMP 2, and the in vitro invasiveness (Matrigel invasion assay) of SKOV-3 and CAOV-3 cells. LY255283 also inhibited the peritoneum metastasis of intra-peritoneal injected SKOV-3 cells in athymic mice.
|
|
However, more severe cases are associated with a more persistent disorder that may be complicated by secondary skin infections and/or involvement of the liver, lung, and/or kidney. Severe cutaneous adverse reaction (SCAR) disorders are regarded as the drug-induced activation of T cells which then initiate innate immune responses that are inappropriately directed against self tissues. Studies on the DRESS syndrome, Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS/TEN overlap indicate that many individuals are predisposed to develop these reactions to a particular medication based on their genetically- determined expression of particular human leukocyte antigen (i.e. HLA) alleles or T-cell receptors and/or their efficiencies in adsorbing, distributing to tissues, metabolizing, and/or eliminating) a particular SCARS-inducing medication.
|
|
Modifications to this flux that may improve ethanol production include deleting the GND1 gene, or the ZWF1 gene. Since the pentose phosphate pathway produces additional NADPH during metabolism, limiting this step will help to correct the already evident imbalance between NAD(P)H and NAD+ cofactors and reduce xylitol byproduct formation. Another experiment comparing the two D-xylose metabolizing pathways revealed that the XI pathway was best able to metabolize D-xylose to produce the greatest ethanol yield, while the XR-XDH pathway reached a much faster rate of ethanol production. Overexpression of the four genes encoding non-oxidative pentose phosphate pathway enzymes Transaldolase, Transketolase, Ribulose-5-phosphate epimerase and Ribose-5-phosphate ketol-isomerase led to both higher D-xylulose and D-xylose fermentation rate.
|
|
Quantitatively, the smooth endoplasmic reticulum of the liver cell is the principal organ of drug metabolism, although every biological tissue has some ability to metabolize drugs. Factors responsible for the liver's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut, and that there are very high concentrations of most drug-metabolizing enzyme systems relative to other organs. If a drug is taken into the GI tract, where it enters hepatic circulation through the portal vein, it becomes well-metabolized and is said to show the first pass effect. Other sites of drug metabolism include epithelial cells of the gastrointestinal tract, lungs, kidneys, and the skin.
|
|
The pharmacogenetics of naproxen has been studied in an effort to better understand its adverse effects. In 1998, a small pharmacokinetic (PK) study failed to show that differences in a patient's ability to clear naproxen from the body could account for differences in a patient's risk of experiencing the adverse effect of a serious gastrointestinal bleed while taking naproxen. However, the study failed to account for differences in the activity of CYP2C9, a drug metabolizing enzyme responsible for clearing naproxen. Studies on the relationship between CYP2C9 genotype and NSAID-induced gastrointestinal bleeds have shown that genetic variants in CYP2C9 that reduce the clearance of major CYP2C9 substrates (like naproxen) increase the risk of NSAID-induced gastrointestinal bleeds, especially for homozygous defective variants.
|
|
"Wild" (as in uninoculated) malolactic ferments have the potential to produce more diacetyl than inoculated ferments due to the lower initial populations during the lag phase with inoculated ferments usually having an initial inoculum of 106 CFU/ml. Late MLF inoculations, after alcoholic fermentation, also tend to produce higher levels of diacetyl. Chardonnay producers desiring to make the high-diacetyl "buttery style" will often do late or "wild" inoculation in the barrel after primary fermentation, allowing the wine to spend several weeks or even months sur lie in reductive conditions that promote diacetyl production. Some sources point out that diacetyl is actually decreased by sur lie, due to surviving yeast metabolizing diacetyl, and therefore malolactic fermentation is best performed apart from lees.
|
|
It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids, DHA acid and EPA, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids. EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases, particularly soluble epoxide hydrolase, and therefore act locally. The fatty acid metabolizing activity, including the ability to form epoxides, of CYP4F12 is very similar to that of CYP4F8. However, it and CYP4F8 are not regarded as being major contributors in forming the cited epoxides in humans although they might do so in tissues where they are highly expressed.
|
|
Economically, Dunaliella, particularly D. salina and D. bardawil, serves great value due to its high accumulation of β-carotenoids. The pigment is exploited for a variety of uses such as cosmetics, natural food-colouring agents, nutritional supplements, and animal feed. It is also used for treating harmful wastewater plants through adsorbing, sequestering, and metabolizing heavy metal ions. Its biotechnological potential has long been exploited ever since it was found that certain species can have up 16% of their dry-weight being composed of β-carotenoids and that lakes and lagoons that turn pink or red, contain very high populations of D. salina that make up as much as 13.8% of the dry organic matter – such as in Pink Lake, Victoria, Australia.
|
|
In humans, the gut flora is established at one to two years after birth; by that time, the intestinal epithelium and the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant to, and even supportive of, the gut flora and that also provides a barrier to pathogenic organisms. The relationship between gut flora and humans is not merely commensal (a non- harmful coexistence), but rather a mutualistic relationship. Human gut microorganisms benefit the host by collecting the energy from the fermentation of undigested carbohydrates and the subsequent absorption of short-chain fatty acids (SCFAs), acetate, butyrate, and propionate. Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics.
|
|
Researchers are working towards building a multi-channel 3D microfluidic cell culture system that compartmentalizes microenvironments in which 3D cellular aggregates are cultured to mimic multiple organs in the body. Most organ-on-a- chip models today only culture one cell type, so even though they may be valid models for studying whole organ functions, the systemic effect of a drug on the human body is not verified. In particular, an integrated cell culture analog (µCCA) was developed and included lung cells, drug-metabolizing liver and fat cells. The cells were linked in a 2D fluidic network with culture medium circulating as a blood surrogate, thus efficiently providing a nutritional delivery transport system, while simultaneously removing wastes from the cells.
|
|
A mutation in codon 450 of M. tuberculosis leads to a minor loss of fitness, while the corresponding mutation in S. aureus results in bacteria barely able to survive. In Neisseria meningitidis rpoB mutations have been observed to increase expression of enzymes which are involved in metabolizing carbohydrates, as well as enzymes involved in the citric acid cycle and in transcription elongation. At the same time enzymes involved in ATP production, cell division, and lipid metabolism are all downregulated, or expressed at a lower than normal level. In M. tuberculosis mutations in the rpoB gene can significantly upregulate polyketide synthase, potentially indicating increased production of phthiocerol dimycocerosate, a lipid produced by M. tuberculosis and implicated in virulence of the bacteria.
|
|
Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics. The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ, and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions. The composition of human gut microbiota changes over time, when the diet changes, and as overall health changes. A systematic review from 2016 examined the preclinical and small human trials that have been conducted with certain commercially available strains of probiotic bacteria and identified those that had the most potential to be useful for certain central nervous system disorders.
|
|
It is noteworthy that epithelial tissue, which makes up lobuloalveolar tissue, normally (outside of pregnancy and lactation) comprises only about 10 to 15% of the tissue of the breasts. Although the influence of progesterone on breast development is uncertain, progesterone is thought to cause reversible breast enlargement during the menstrual cycle due to local fluid retention in the breasts. This may give a misleading appearance of breast growth, and might contribute to anecdotal reports of improved breast size and/or shape with progesterone in transgender women. Progestogens have some antiestrogenic effects in the breasts, for instance decreasing expression of the estrogen receptor and increasing expression of estrogen-metabolizing enzymes, and for this reason, have been used to treat breast pain and benign breast disorders.
|
|
He studied for his PhD in Agriculture Entomology at the Kansas State University and specialized in Grain Science Technology. He did a year of post-doctoral work in the Department of Entomology, Texas A&M; University, (1969), on problems related to isolation and purification of polyhedral virus (6). He joined University of Minnesota in 1970 as a faculty in the Department of Entomology, Fisheries and Wildlife. He worked on isolation and characterization fungal toxins (10,11). He joined Prof Marion Andrews in the Department of Pharmacology in 1971 and worked on drug metabolizing enzymes (12,13). In 1972 he started working with James G White in the Department of Pediatrics, who was working on the morphology and ultra structure of blood platelets.
|
|
1,500 additional citations. The S&S; algorithm has thus significantly impacted the field of medicine, and is increasingly applied in today's disease research, pharmacogenomics, and Precision Medicine, as up to 50% of all diseases and ADRs (Adverse Drug Reactions) are now thought to be caused by RNA splicing mutations. Using the S&S; algorithm, scientists have identified mutations and genes that cause numerous cancers, inherited disorders, immune deficiency diseases and neurological disorders. In addition, mutations in various drug metabolizing genes that cause ADRs to different drugs that are used to treat different diseases, including cancer chemotherapeutic drugs, have been identified. S&S; is also used in detecting the “cryptic” splice sites that are not authentic sites used in the normal splicing of gene transcripts, and the mutations in which cause numerous diseases.
|
|
As metabolite analyses are being conducted at the individual patient level, pharmacometabolomics may be considered a form of personalized medicine. This field is currently being employed in a predictive manner to determine the potential responses of therapeutic compounds in individual patients, allowing for more customized treatment regimens. It is anticipated that such pharmacometabolomics approaches will lead to the improved ability to predict an individual's response to a compound, the efficacy and metabolism of it as well as adverse or off-target effects that may take place in the body. The metabolism of certain drugs varies from patient to patient as the copy number of the genes which code for common drug metabolizing enzymes varies within the population, and leads to differences in the ability of an individual to metabolize different compounds.
|
|
His work served as the foundation for the concept of in vitro activation of procarcinogens to substances that damage DNA, which was the basis for a widely used test of chemicals for their cancer-producing potential (the Ames test). His laboratory was the first to introduce high- performance liquid chromatography to the study of metabolism (chemical conversions in the body) of certain hazardous chemicals to which people may be exposed. His work had a huge impact on the fields of chemical carcinogenesis, drug and carcinogen metabolism, and on studies of the cytochrome P-450 drug and carcinogen metabolizing enzymes. During his career at NIH, Gelboin received numerous awards, including four NIH Merit awards, a technology transfer award, an honorary D.Sc. degree, a Nakasone Lecture Award and a Claude Bernard Award.
|
|
Nicotine is poisonous to most animals that use muscles to move because nicotine targets the acetylcholine receptor at the neuromuscular junction. However, the tobacco hornworm is capable of metabolizing nicotine from the tobacco plant and using nicotine as a defense against predators. It possesses a gene called cytochrome P450 6B46 (CYP6B46) that converts nicotine into a metabolite. About 0.65% of nicotine metabolites are transported from the gut to the hemolymph, where they are reconverted to nicotine and released into the air from the tobacco hornworm's spiracles. The emitted nicotine is used as a way to deter spiders, a practice known as “toxic halitosis.” In one study, tobacco hornworms that fed from nicotine-deficient plants or expressed low levels of CYP6B46 were more susceptible to wolf spider predation (Kumar et al.
|
|
5,6-EEQ isomers are generally either not formed or formed in undetectable amounts while 8,9-EEQ isomers are formed in relatively small amounts by the cited CYPs. The EET-forming CYP epoxygenases often metabolize EPA to EEQs (as well as DHA to EDPs) at rates that exceed their rates in metabolizing arachidonic acid to EETs; that is, EPA (and DHA) appear to be preferred over arachidonic acid as substrates for many CYP epoxygenases. The EEQ-forming cytochromes are widely distributed in the tissues of humans and other mammals, including blood vessel endothelium, blood vessel atheroma plaques, heart muscle, kidneys, pancreas, intestine, lung, brain, monocytes, and macrophages. These tissues are known to metabolize arachidonic acid to EETs; it has been shown or is presumed that they also metabolize EPA to EEQs.
|
|
1,4-Butanediol is converted into GHB by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase, and differing levels of these enzymes may account for differences in effects and side effects between users. While co-administration of ethanol and GHB already poses serious risks, co-administration of ethanol with 1,4-butanediol will interact considerably and has many other potential risks. This is because the same enzymes that are responsible for metabolizing alcohol also metabolize 1,4-butanediol so there is a strong chance of a dangerous drug interaction. Emergency room patients who overdose on both ethanol and 1,4-butanediol often present with symptoms of alcohol intoxication initially and as the ethanol is metabolized the 1,4-butanediol is then able to better compete for the enzyme and a second period of intoxication ensues as the 1,4-butanediol is converted into GHB.
|
|
Human EH3 is a recently characterized protein with epoxy hydrolase activity for metabolizing epoxyeicosatrienoic acids (EETs) and vernolic acids (leukotoxins) to their corresponding diols; in these capacities they may thereby limit the cell signaling activity of the EETs and contribute to the toxicity of the leukotoxins. mRNA for EH3 is most strongly expressed in the lung, skin, and upper gastrointestinal tract tissues of mice. The function of EH3 in humans, mice, or other mammals has not yet been determined although the gene for EH3 has been validated as being hypermethylated on CpG sites in its promoter region in human prostate cancer tissue, particularly in the tissues of more advanced or morphologically-based (i.e. Gleason score) more aggressive cancers; this suggests that the gene silencing of EH3 due to this hypermethylation may contribute to the onset and/or progression of prostate cancer.
|
|
CYP4A22 (cytochrome P450, family 4, subfamily A, polypeptide 22) also known as fatty acid omega-hydroxylase is a protein which in humans is encoded by the CYP4A22 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. This gene is part of a cluster of cytochrome P450 genes on chromosome 1p33. CYP4A22 was once considered, along with CYP4A11, CYP4F2, and CYP4F3, as active in metabolizing arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) by an omega oxidation reaction with the predominant 20-HETE-synthesizing enzymes in humans being CYP4F2 followed by CYP4A11; 20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans.
|
|
The prevalence of ethanol-induced allergic symptoms in non-Asian genotypes commonly ranges above 5% even though many of these non-Asian populations have no or very low levels of individuals bearing the glu487lys allele. These "ethanol reactors" may have other gene-based abnormalities that cause the accumulation of acetaldehyde following the ingestion of ethanol or ethanol- containing beverages. For example, the surveyed incidence of self-reported ethanol-induced flushing reactions in Scandinavians living in Copenhagen as well as Australians of European descent is about ~16% in individuals homozygous for the "normal" ADH1B gene but runs to ~23% in individuals with the ADH1-Arg48His Single-nucleotide polymorphism variant; in vitro, this variant metabolizes ethanol rapidly and, it is proposed but not proven, in humans forms acetaldehyde at levels exceeding ALDH2's acetaldehyde- metabolizing capacity.Int Arch Allergy Immunol. 2010;153(1):86-94.
|
|
CYP2J2 localizes to the endoplasmic reticulum and is thought to be a prominent enzyme responsible for metabolizing endogenous polyunsaturated fatty acids to signaling molecules. It metabolizes arachidonic acid to the following eicosatrienoic acid epoxides (termed EETs): 5,6-epoxy-8Z,11Z,14Z-EET, 8,9-epoxy-8Z,11Z,14Z-EET, 11,12-epoxy-5Z,8Z,14Z-EET, and 14,15-epoxy-5Z,8Z,11Z-EET. CYP2J2 also metabolizes linoleic acid to 9,10-epoxy octadecaenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecaenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs). CYP2J2, along with CYP219, CYP2C8, CYP2C9, and possibly CYP2S1 are the main producers of EETs and, very likely EEQs, EDPs, and the epoxides of linoleic acid.
|
|
Myristicin has also been shown to inhibit cytochrome P450 enzymes in humans, which is responsible for metabolizing a variety of substrates including hormones and toxins, allowing these substrates to accumulate. This can compound its own toxicity and/or lead to increased bioavailability of other substances, which can lower the threshold for overdose from other drugs that may be in the body. The effects of nutmeg consumed in large doses are attributed mostly to myristicin, where 1–7 hours following ingestion symptoms include disorientation, giddiness, stupor, and/or stimulation of the central nervous system leading to euphoria, intense hallucinations that alter one's orientation to time and surroundings, feelings of levitation, loss of consciousness, tachycardia, weak pulse, anxiety, and hypertension. Symptoms of nutmeg intoxication further include nausea, abdominal pain, vomiting, dryness of mouth, mydriasis or miosis, hypotension, shock, and potentially death.
|
|
The advantages of working with an SPMD passive sampler as opposed to a normal field test with an organism are that SPMDs are able to be deployed in extremely toxic waters that might be too toxic for an organism to live in or just not inhabited by sessile filter feeders. The design of the SPMD makes it so that it imitates the process of accumulating contaminants the way a mussel or oyster would, but without the issues of mortality or metabolizing any contaminants that may be present. They can also be deployed for a long period of time and can account for surge runoff events, chemical spills or other abnormal pollution events. The physical structure of a SPMD with its stainless steel covering protects it and allows it to be suspended on a sessile anchor in the water column.
|
|
15-lipoxygenase 1 (ALOX15), while best known for converting the 20 carbon polyunsaturated fatty acid, arachidonic acid, into a series of 15-hydroxylated arachidonic acid metabolites (see 15-hydroxyicosatetraenoic acid), actually prefers as its substrate the 18 carbon polyunsaturated fatty acid, linoleic acid, over arachidonic acid, converting it to 13-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE). The enzyme acts in a highly stereospecific manner, forming 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13(S)-HpODE) but comparatively little or no 13(R)-hydroperoxy-9Z,11E-octadecadienoic acid (13(R)-HpODE) -. In cells, 13(S)-HpODE is rapidly reduced by peroxidases to 13(S)-HODE. ALOX15 is fully capable of metabolizing the linoleic acid that is bound to phospholipid or cholesterol to form 13(S)-HpODE-bound phospholipids and cholesterol that are rapidly converted to their corresponding 13(S)-HODE-bound products.
|
|
However this enzyme has a preference for metabolizing linoleic acid rather than arachidonic acid. It therefore forms linoleic acid metabolites (e.g. 13-hydoxyperoxy/hydroxy- octadecadienoic and 9-hydroperoxy/hydroxyl-octadecadienoic acids) in greater amounts than 15(S)-HpETE and 15(S)-HETE. 15-LOX-2 also differs from 15-LOX-1 in that it does not make 12(S)-HpETE or the leukotriene A4 isomer cited above. Cycloxygenase: Cells can use prostaglandin-endoperoxide synthase 1 (i.e. cyclooxygenenase-1 or COX-1) and Prostaglandin-endoperoxide synthase 2 (COX-2) to metabolize arachidonic acid primarily to prostaglandins but also to small amounts of 11(R)-HETE and a racemic mixture of 15-HETEs composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE. When pretreated with aspirin, however, COX-1 is inactive while COX-2 attacks arachidonic acid to produce almost exclusively 15(R)-HETE along with its presumed precursor 15(R)-HpETE.
|
|
Structure showing the amino acid residues that degrade under UVR exposure. Shown are Tryptophan-81, Cysteine-223, Cysteine-229, Tryptophan-234, Methionine-295 and Methionine-366 ALDH3A1 comprises approximately 10-40% of the water-soluble protein in the mammalian cornea. Direct exposure to UVR and molecular oxygen, make the cornea susceptible to ROS and 4HNE. Studies in which rabbits were transfected with genes that allow them to overexpress human ALDH3A1 in their corneal stromal fibroblasts document ALDH3A1's most critical function is to protect the cornea from oxidative stresses. In the cornea ALDH3A1: (1) prevents the formation of 4-HNE protein adducts that would impeded proteins’ function; (2) is more effective at metabolizing 4-HNE than other comparable agents such as glutathione (GSH); (3) protects the corneal cells from 4-HNE induced apoptosis; (4) reduces consumption of GSH by relieving 4HNE GSH adducts; (5) and relieves 4-HNE's inhibition of the 20S protease activity.
|
|
The cytochrome P450s (P450s) are xenobiotic-metabolizing membrane- bound heme-containing enzymes that use molecular oxygen and electrons from NADPH cytochrome P450 reductase to oxidize their substrates. CYP2B4, a member of the cytochrome P450 family is the only protein within this family, whose X-ray structure in both open 11 and closed form 12 is published. The comparison of the open and closed structures of CYP2B4 structures reveals large-scale conformational rearrangement between the two states, with the greatest conformational change around the residues 215-225, which is widely open in ligand-free state and shut after ligand binding; and the region around loop C near the heme. HB Plot and structure of Cytochrome P450 2B4 in closed form Examining the HB plot of the closed and open state of CYP2B4 revealed that the rearrangement of tertiary hydrogen bonds was in excellent agreement with the current knowledge of the cytochrome P450 catalytic cycle.
|
|
Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX), is the key enzyme in prostaglandin biosynthesis. It converts free arachidonic acid, released from membrane phospholipids at the sn-2 ester binding site by the enzymatic activity of phospholipase A2, to prostaglandin (PG) H2. The reaction involves both cyclooxygenase (dioxygenase) and hydroperoxidase (peroxidase) activity. The cyclooxygenase activity incorporates two oxygen molecules into arachidonic acid or alternate polyunsaturated fatty acid substrates, such as linoleic acid and eicosapentaenoic acid. Metabolism of arachidonic acid forms a labile intermediate peroxide, PGG2, which is reduced to the corresponding alcohol, PGH2, by the enzyme’s hydroperoxidase activity. While metabolizing arachidonic acid primarily to PGG2, COX-1 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids (i.e., 15-HETEs) composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE stereoisomers as well as a small amount of 11(R)-HETE. The two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more importantly, can be further metabolized to a major class of anti-inflammatory agents, the lipoxins.
|
|
ALOX12B oxygenates arachidonic acid by adding molecular oxygen (O2) in the form of a hydroperoxyl (HO2) residue to its 12th carbon thereby forming 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (also termed 12(R)-HpETE or 12R-HpETE). When formed in cells, 12R-HpETE may be quickly reduced to its hydroxyl analog (OH), 12(R)-hydroxy-5'Z,8Z,10E,14Z-eicosatetraenoic acid (also termed 12(R)-HETE or 12R-HETE), by ubiquitous peroxidase-type enzymes. These sequential metabolic reactions are: arachidonic acid + O2 \rightleftharpoons 12R-HpETE → 12R-HETE 12R-HETE stimulates animal and human neutrophil chemotaxis and other responses in vitro and is able to elicit inflammatory responses when injected into the skin of an animal model However, the production of 12R-HETE for this or other purposes may not be primary function of ALOX12B. ALOX12B is also capable of metabolizing free linoleic acid to 9(R)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HpODE) which is also rapidly converted to its hydroxyl derivative, 9-Hydroxyoctadecadienoic acid (9R-HODE).
|
|
CYP2C9 and CYP2S1 are known to, and many or all of the other CYPs that act on arachidonic acid are thought to, metabolize the 18 carbon essential fatty acid, 9(Z),12(Z)-octadecadienoic acid, i.e. linoleic acid, at is 12,13 carbon-carbon double bout to form (+) and (-) epoxy optical isomers viz., the 9S,10R-epoxy-12(Z)-octadecaenoic and 9R,10S-epoxy-12(Z)-octadecaenoic acids; this set of optical isomers is also termed vernolic acid, linoleic acid 9:10-oxide, and leukotoxin. CYPC2C9 is known and the other arachidonic acid-metabolizing CYPs are thought to likewise attack linoleic acid at its 9,10 carbon-carbon double bound to form 12S,13R-epoxy-9(Z)-octadecaenoic and 12R,13S-epoxy-9(Z)-octadecaenoic acid optical isomers; this set of optical isomers is also termed coronaric acid, linoleic acid 12,13-oxide, and isoleukotoxin These linoleic acid-derived leukotoxin and isoleukotoxin sets of optical isomers possess activities similar to that of other leukotoxins such as the pore-forming leukotoxin family of RTX toxin virulence factor proteins secreted by gram-negative bacteria, e.g.
|
|
In colorectal, breast, and kidney cancers, 15-LOX-1 levels are low or absent compared to the cancers' normal tissue counterparts and/or these levels sharply decline as the cancers progress. These results, as well as a 15-LOX-1 transgene study on colon cancer in mice suggests but do not prove that 15-LOX-1 is a tumor suppressor. By metabolizing ω-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into lipoxins and resolvins, 15-LOX-1 is thought to be one mechanism by which dietary ω-3 polyunsaturated fatty acids, particularly fish oil, may act to reduce the incidence and/or progression of certain cancers. Indeed, the ability of docosahexaenoic acid to inhibit the growth of cultured human prostate cancer cells is totally dependent upon the expression of 15-LOX-1 by these cells and appears due to this enzyme's production of docosahexaenoic acid metabolites such as 17(S)-HpETE, 17(S)-HETE, and/or and, possibly, an isomer of protectin DX (10S, 17S-dihydroxy-4Z, 7Z, 11E, 13Z, 15E, 19Z-docosahexaenoic acid) Kelavkar et.
|
|
Both compounds are members of the specialized proresolving mediators class of PUFA metabolites in that they possess potent anti-inflammatory activity; however, only PDX inhibited human platelet aggregation responses. Subsequent studies found that various other dihydroxy-E,Z,E-double bound-configured PUFA but not those with E,E,E or E,E,Z double bond configurations share with PDX anti-platelet activity. Cells make PDX by metabolizing DHA by double oxygenation a 15-lipoxygenase to form the 10R,17S-hydroxperoxy intermediated which is reduced its 10R,17S-hydroxyl product, PDX, probably by cytosolic GPX1 (i.e. glutathione peroxidase 1). Serial metabolism two different lipoxygenases or a lipoxygenase and a cytochrome P45) on PUFA possessing three double bonds in a 1Z,4Z,7Z configuration may also make a 1,7-dihydroxy 2E,4Z,6E product. Other platelet- inhibiting dihydroxy-E,Z,E-PUFA are: 10R,17S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (10R,17S-diHDHA); 8S,15S-dihydroxy-5Z,9E,11Z,13E-eicosatetraenoic acid (8S,15S-diHETE); 9S,16S-10E,12Z,14E-octadecatrienoic acid (linotrin-1); and 9R,16S-10E,12Z,14E-octadecatrienoic acid (linotrin-2).
|
|
The enzymes cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), which are best known for metabolizing arachidonic acid to prostaglandins, are also able to metabolize linoleic acid predominantly to 9(R)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (i.e. 9(R)-HpODE)-HODE) and lesser amounts of 9(S)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (i.e. 9(S)-HpODE); in cells and tissues, the two hydroperoxy metabolites are rapidly reduce to 9(R)-HODE and 9(S)-HODE, respectively.J Biol Chem. 1995 Aug 18;270(33):19330-6J Invest Dermatol. 1996 Nov;107(5):726-32rch Biochem Biophys. 1998 Jan 15;349(2):376-80 COX-2 exhibits a greater preference for linoleic acid than does Cox-1 and is therefore credited with producing most of these products in cells expressing both COX enzymes. The COXs also metabolize linoleic acid to 13(S)-hydroperoxy-octadecadionoic acid (13(S)-HpODE and lesser amounts of 13(R)-hydroperoxy-octadecadienoic acid (13(R)-HpODE, which are then rapidly reduced to 13(S)-HODE) and 13(R)-HODE; the two enzymes therefore metabolize linoleic acid predominantly to the R stereoisomer of 9-HODE and (S) stereoisomer of 13-HODE with the 13-HODE products predominating over the 9-HODE products.Prostaglandins.
|
|