cyp2c8 cyp2c8 cytochrome p4502c8 (cyp2c8) is a member of the cytochrome p450 mixed-function oxidase system 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. cyp2c8available structurespdbortholog search: pdbe rcsb list of pdb id codes2vn0, 1pq2, 2nnh, 2nni, 2nnjidentifiersaliasescyp2c8, cpc8, cypiic8, mp-12/mp-20, cytochrome p450 family 2 subfamily c member 8, cyp2c8dmexternal idsomim: 601129 mgi: 1306818 homologene: 117948 genecards: cyp2c8 gene location (human)chr.chromosome 10 (human)band10q23.33start95,036,772 bpend95,069,497 bpgene location (mouse)chr.chromosome 19 (mouse)band19|19 c3start39,499,306 bpend39,556,973 bprna expression patternbgeehumanmouse (ortholog)top expressed inright lobe of liverspermpancreatic ductal cellright uterine tubegallbladderanterior pituitarybody of stomachbody of pancreasbronchial epithelial cellbrodmann area 9top expressed inliverthoracic diaphragmmore reference expression databiogpsmore reference expression datagene ontologymolecular function oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen caffeine oxidase activity aromatase activity oxidoreductase activity heme binding metal ion binding iron ion binding arachidonic acid epoxygenase activity monooxygenase activity estrogen 16-alpha-hydroxylase activity steroid hydroxylase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen cellular component endoplasmic reticulum organelle membrane membrane intracellular membrane-bounded organelle endoplasmic reticulum membrane cytoplasm biological process omega-hydroxylase p450 pathway organic acid metabolic process epoxygenase p450 pathway oxidative demethylation xenobiotic metabolic process lipid hydroxylation steroid metabolic process long-chain fatty acid biosynthetic process estrogen metabolic process sources:amigo / quickgoorthologsspecieshumanmouseentrez155813098ensemblensg00000138115ensmusg00000025003uniprotp10632p56656refseq (mrna)nm_000770nm_001198853nm_001198854nm_001198855nm_030878nm_010003nm_001373937refseq (protein)np_000761np_001185782np_001185783np_001185784np_034133np_001360866location (ucsc)chr 10: 95.04 – 95.07 mbchr 19: 39.5 – 39.56 mbpubmed searchwikidataview/edit humanview/edit mouse 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. selected inducers, inhibitors and substrates of cyp2c8 substratesinhibitorsinducers amodiaquine (antimalarial, anti-inflammatory) cerivastatin (statin) enzalutamide (antiandrogen) paclitaxel (chemotherapeutic) repaglinide (antidiabetic) torasemide (loop diuretic) sorafenib (tyrosine kinase inhibitor) rosiglitazone (antidiabetic) - converted to active metabolites buprenorphine (semisynthetic opioid) polyunsaturated fatty acids montelukast (leukotriene receptor antagonist) strong gemfibrozil (hypolipidemic) the acyl-β-glucuronide metabolite of clopidogrel (antiplatelet) moderate trimethoprim (antibiotic) unspecified potency thiazolidinediones (antidiabetic) montelukast (leukotriene receptor antagonist) quercetin (antiinflammatory) unspecified potency rifampicin (antibiotic) where classes of agents are listed, there may be exceptions within the class. epoxygenase activity cyp2c8 also possesses epoxygenase activity: it is one of the principal enzymes responsible for attacking 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 octadecenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); 3) docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed edps); and 4) eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed eeqs). along with cyp2c8, cyp2c9, cyp2c19, cyp2j2, and possibly cyp2s1 are the main producers of eets and, very likely, eeqs, edps, and the epoxides of linoleic acid.