Microsomal Ethanol-oxidizing System
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Microsomal Ethanol-oxidizing System
Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals. While CYP2E1 itself carries out a relatively low number of these reactions (~4% of known P450-mediated drug oxidations), it and related enzymes CYP1A2 and CYP3A4 are responsible for the breakdown of many toxic environmental chemicals and carcinogens that enter the body, in addition to basic metabolic reactions such as fatty acid oxidations. Function CYP2E1 is a membrane protein expressed in high levels in the liver, where it composes nearly 50% of the total hepatic cytochrome P450 mRNA and 7% of the hepatic cytochrome P450 protein. The liver is therefore where most drugs undergo deactivation by CYP2E1, either directly ...
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Cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance (pharmacology), clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Ronald W. Estabrook, Estabrook, David Y. Cooper, Cooper, and Otto Rosenthal, Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of secondary metabolite, defensive compounds, fatty acids, and hormones. CYP enzymes have been identified in all kingdom (biology), kingdoms of life: animals, plants, fungus, fungi, protists, bacteria, and archaea, as well as in viruses. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. , more than 300,000 distinct CYP proteins ...
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Acetyl-CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol). CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and ...
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Arteriole
An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles have muscular walls (usually only one to two layers of smooth muscle cells) and are the primary site of vascular resistance. The greatest change in blood pressure and velocity of blood flow occurs at the transition of arterioles to capillaries.This function is extremely important because it prevents the thin, one-layer capillaries from exploding upon pressure. The arterioles achieve this decrease in pressure, as they are the site with the highest resistance (a large contributor to total peripheral resistance) which translates to a large decrease in the pressure. Structure Microanatomy In a healthy vascular system the endothelium lines all blood-contacting surfaces, including arteries, arterioles, veins, venules, capillaries, and heart chambers. This healthy condition is promoted by the ample production of nitric oxide by the end ...
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Eicosapentaenoic Acid
Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-carbon chain and five ''cis'' double bonds; the first double bond is located at the third carbon from the omega end. EPA is a polyunsaturated fatty acid (PUFA) that acts as a precursor for prostaglandin-3 (which inhibits platelet aggregation), thromboxane-3, and leukotriene-5 eicosanoids. EPA is both a precursor and the hydrolytic breakdown product of eicosapentaenoyl ethanolamide (EPEA: C22 H35 NO2; 20:5,n-3). Although studies of fish oil supplements, which contain both docosahexaenoic acid (DHA) and EPA, have failed to support claims of preventing heart attacks or strokes, a recent multi-year study of Vascepa ( ethyl eicosapentaenoate, the ethyl ester of the free fatty acid), a prescription drug containing only EPA, was shown to re ...
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Epoxide
In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale for many applications. In general, low molecular weight epoxides are colourless and nonpolar, and often volatile. Nomenclature A compound containing the epoxide functional group can be called an epoxy, epoxide, oxirane, and ethoxyline. Simple epoxides are often referred to as oxides. Thus, the epoxide of ethylene (C2H4) is ethylene oxide (C2H4O). Many compounds have trivial names; for instance, ethylene oxide is called "oxirane". Some names emphasize the presence of the epoxide functional group, as in the compound ''1,2-epoxyheptane'', which can also be called ''1,2-heptene oxide''. A polymer formed from epoxide precursors is called an ''epoxy'', but such materials do not contain epoxide groups (or contain only a few residual epoxy grou ...
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Docosahexaenoic Acid
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk (breast milk), fatty fish, fish oil, or algae oil. DHA's structure is a carboxylic acid (-''oic acid'') with a 22-carbon chain (''docosa-'' derives from the Ancient Greek for 22) and six (''hexa-'') ''cis'' double bonds (''-en-''); with the first double bond located at the third carbon from the omega end. Its trivial name is cervonic acid (from the Latin word ''cerebrum'' for "brain"), its systematic name is ''all-cis''-docosa-4,7,10,13,16,19-hexa-enoic acid, and its shorthand name is 22:6(n−3) in the nomenclature of fatty acids. Most of the docosahexaenoic acid in fish and multi-cellular organisms with access to cold-water oceanic foods originates from photosynthetic and heterotroph ...
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Epoxygenase
Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 (CYP P450 or just CYP) enzymes that metabolize polyunsaturated fatty acids to epoxide products that have a range of biological activities. The most thoroughly studied substrate of the CYP epoxylgenases is arachidonic acid. This polyunsaturated fatty acid is metabolized by cyclooxygenases to various prostaglandin, thromboxane, and prostacyclin metabolites in what has been termed the first pathway of eicosanoid production; it is also metabolized by various lipoxygenases to hydroxyeicosatetraenoic acids (e.g. 5-Hydroxyeicosatetraenoic acid, 12-Hydroxyeicosatetraenoic acid, 15-hydroxyicosatetraenoic acid) and leukotrienes (e.g. leukotriene B4, leukotriene C4) in what has been termed the second pathway of eicosanoid production. The metabolism of arachidonic acid to epoxyeicosatrienoic acids by the CYP epoxygenases has been termed the third pathway of eicosanoid metabolism. Like the first two pathways of eic ...
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20-Hydroxyeicosatetraenoic Acid
20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5''Z'',8''Z'',11''Z'',14''Z''-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regulation of vascular tone, blood flow to specific organs, sodium and fluid transport in the kidney, and vascular pathway remodeling. These vascular and kidney effects of 20-HETE have been shown to be responsible for regulating blood pressure and blood flow to specific organs in rodents; genetic and preclinical studies suggest that 20-HETE may similarly regulate blood pressure and contribute to the development of stroke and heart attacks. Additionally the loss of its production appears to be one cause of the human neurological disease, Hereditary spastic paraplegia. Preclinical studies also suggest that the overproduction of 20-HETE may contribute to the progression of certain human cancers, particularly those of the breast. Biosynthesis ...
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Arachidonic Acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachis'' (peanut), but peanut oil does not contain any arachidonic acid. Chemistry In chemical structure, arachidonic acid is a carboxylic acid with a 20-carbon chain and four ''cis''-double bonds; the first double bond is located at the sixth carbon from the omega end. Some chemistry sources define 'arachidonic acid' to designate any of the eicosatetraenoic acids. However, almost all writings in biology, medicine, and nutrition limit the term to ''all cis''-5,8,11,14-eicosatetraenoic acid. Biology Arachidonic acid is a polyunsaturated fatty acid present in the phospholipids (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositides) of membranes of the body's cells, and is abundant in the brain, muscles, an ...
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Lactic Acid
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natural sources. Lactic acid is an alpha-hydroxy acid (AHA) due to the presence of a hydroxyl group adjacent to the carboxyl group. It is used as a synthetic intermediate in many organic synthesis industries and in various biochemical industries. The conjugate base of lactic acid is called lactate (or the lactate anion). The name of the derived acyl group is lactoyl. In solution, it can ionize by loss of a proton to produce the lactate ion . Compared to acetic acid, its p''K'' is 1 unit less, meaning lactic acid is ten times more acidic than acetic acid. This higher acidity is the consequence of the intramolecular hydrogen bonding between the α-hydroxyl and the carboxylate group. Lactic acid is chiral, consisting of two enantiomers. One ...
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Pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or to fatty acids through a reaction with acetyl-CoA. It can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation. Pyruvic acid supplies energy to cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present (aerobic respiration), and alternatively ferments to produce lactate when oxygen is lacking. Chemistry In 1834, Théophile-Jules Pelouze distilled tartaric acid and isolated glutaric acid and another unknown organic acid. Jöns Jacob Berzelius characterized this other acid the following year and named pyruvic acid because it ...
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Methylglyoxal
Methylglyoxal (MGO) is the organic compound with the formula CH3C(O)CHO. It is a reduced derivative of pyruvic acid. It is a reactive compound that is implicated in the biology of diabetes. Methylglyoxal is produced industrially by degradation of carbohydrates using overexpressed methylglyoxal synthase. Chemical structure Gaseous methylglyoxal has two carbonyl groups, an aldehyde and a ketone. In the presence of water, it exists as hydrates and oligomers. The formation of these hydrates is indicative of the high reactivity of MGO, which is relevant to its biological behavior. Biochemistry Biosynthesis and biodegradation In organisms, methylglyoxal is formed as a side-product of several metabolic pathways. Methylglyoxal mainly arises as side products of glycolysis involving glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. It is also thought to arise via the degradation of acetone and threonine. Illustrative of the myriad pathways to MGO, aristolochic acid caused 12-f ...
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