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Epoxyeicosatetraenoic Acid
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. Structure EPA is a straight-chain, 20 carbon omega-3 fatty acid containing cis (see Cis–trans isomerism) double bonds between carbons 5 and 6, 8 and 9, 11 and 12, 14 and 15, and 17 and 18; each of these double bonds is designated with the notation ''Z'' to indicate its cis configuration in the IUPAC Chemical nomenclature used here. EPA is therefore 5''Z'',8''Z'',11''Z'',14''Z'',17''Z''-eicosapentaenoic acid. Certain cytochrome P450 epoxygenases metabolize EPA by converting one of these double bounds to an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epoxides
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP4F8
Cytochrome P450 4F8 is a protein that in humans is encoded by the ''CYP4F8'' gene. Function This gene, CYP4F8, 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 protein localizes to the endoplasmic reticulum and functions as a 19-hydroxylase of the arachidonic acid metabolite, prostaglandin H2 (PGH2) and the Dihomo-γ-linolenic acid metabolite PGH1 in seminal vesicles. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F3, is approximately 18 kb away. In addition to seminal vesicles, CYP4F8 is expressed in kidney, prostate, epidermis, and corneal epithelium, and its mRNA has been found in retina; CYP4F8 is also greatly up-regulated in psoriatic skin. In addition to its ability to metabolize and presumably thereby to inactivate or reduce the ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP4A11
Cytochrome P450 4A11 is a protein that in humans is codified by the ''CYP4A11'' gene. Function 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 protein localizes to the endoplasmic reticulum and hydroxylates medium-chain fatty acids such as laurate and myristate. CYP4A11 is highly expressed in the liver and kidney. CYP4A11 along with CYP4A22, CYP4F2, and CYP4F3 metabolize 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. Gene polymorphism variants of CYP4A11 are associated with the development of hypertension and cere ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2S1
Cytochrome P450 2S1 is a protein that in humans is encoded by the ''CYP2S1'' gene. The gene is located in chromosome 19q13.2 within a cluster including other CYP2 family members such as CYP2A6, CYP2A13, CYP2B6, and CYP2F1. Expression CYP2S1 is highly expressed in epithelial tissues of the respiratory, gastrointestinal, urinary tracts, and skin and in leukocytes of the monocyte/macrophage and lymphocyte series; it is also expressed throughout Embryogenesis and, as discussed below, certain types of cancers. Function 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 protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens although its specific function(s) in humans has not been clearly determined. In in vitro stud ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme. While many drugs are deactivated by CYP3A4, there are also some drugs which are ''activated'' by the enzyme. Some substances, such as some drugs and furanocoumarins present in grapefruit juice, interfere with the action of CYP3A4. These substances will therefore either amplify or weaken the action of those drugs that are modified by CYP3A4. CYP3A4 is a member of the cytochrome P450 family of oxidizing enzymes. Several other members of this family are also involved in drug metabolism, but CYP3A4 is the most common and the most versatile one. Like all members of this family, it is a hemoprotein, i.e. a protein containing a heme group with an iron atom. In humans, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2J2
Cytochrome P450 2J2 (CYP2J2) is a protein that in humans is encoded by the ''CYP2J2'' gene. CYP2J2 is a member of the cytochrome P450 superfamily of enzymes. The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as in the synthesis of cholesterol, steroids and other lipids. Protein structure The CYP2J2 contains the following domains: • Hydrophobic binding domains • F-G loop (containing non-conservative mutations) primary membrane binding motif The protein also contains an N-terminal anchor. F-G loop The F-G loop mediates the binding and passage of substrates, and its hydrophobic region containing residues Trp-235, Phe-239 and Ille-236 allows the enzyme to interact with cellular membranes. Mutations to hydrophilic residues in the F-G loop alter the binding mechanism by changing insertion depth of the enzyme into the membrane. Tissue distribution CYP2J2 is expressed predominately in the heart and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2E1
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 o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2C19
Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the ''CYP2C19'' gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam. CYP2C19 has been annotated as (R)-limonene 6-monooxygenase and (S)-limonene 6-monooxygenase in UniProt. Function The gene encodes a member of the cytochrome P450 superfamily of enzymes. Enzymes in the CYP2C subfamily, including CYP2C19, account for approximately 20% of cytochrome P450 in the adult liver. These pro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2C18
Cytochrome P450 2C18 is a protein that in humans is encoded by the ''CYP2C18'' gene. Function 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 protein localizes to the endoplasmic reticulum but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP4217 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19. CYP2C18 also possesses epoxygenase activity: it can attack various long-chain polyunsaturated fatty acids at their double (i.e. alkene) bonds to form epoxide products that act as signaling agents. It metabolizes: 1) arachidonic acid to various epoxyeicosatrienoic acids (also termed EETs); 2) linoleic acid to 9,10-epoxy o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2C9
Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the ''CYP2C9'' gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme. Function CYP2C9 is a crucial cytochrome P450 enzyme, which plays a significant role in the metabolism, by oxidation, of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes. The protein is mainly expressed in liver, duodenum and small intestine. About 100 therapeutic drugs are metabolized by CYP2C9, including drugs with a narrow therapeutic index such as warfarin and phenytoin, and other routinely prescribed drugs such as acenocoumarol, tolbutamide, losartan, glipizide, and some nonsteroidal anti-inflammatory drugs. By contrast, the known extr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2C8
Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsaturated fatty acids, e.g. arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and Linoleic acid to their biologically active epoxides. Ligands Following is a table of selected substrates, inducers and inhibitors of 2C8. Inhibitors of CYP2C8 can be classified by their potency, such as: *Strong inhibitor being one that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance. *Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance. *Weak inhibitor being one that causes at least a 1.25-fold but less than two-fold increase in the plasma AUC values, or 20-50% decrease in clearance. Retrieved on July ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
