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.^[5]

CYP2C8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2VN0, 1PQ2, 2NNH, 2NNI, 2NNJ
Identifiers
Aliases	CYP2C8, CPC8, CYPIIC8, MP-12/MP-20, cytochrome P450 family 2 subfamily C member 8, CYP2C8DM
External IDs	OMIM: 601129; MGI: 1306818; HomoloGene: 117948; GeneCards: CYP2C8; OMA:CYP2C8 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q23.33 Start 95,036,772 bp[1] End 95,069,497 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 C3 Start 39,499,306 bp[2] End 39,556,973 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver sperm pancreatic ductal cell right uterine tube testicle gallbladder anterior pituitary left adrenal cortex gonad body of stomach Top expressed in liver thoracic diaphragm More reference expression data BioGPS More reference expression data
Gene ontology Molecular 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 / QuickGO
Orthologs Species Human Mouse Entrez 1558 13098 Ensembl ENSG00000138115 ENSMUSG00000025003 UniProt P10632 P56656 RefSeq (mRNA) NM_000770 NM_001198853 NM_001198854 NM_001198855 NM_030878 NM_010003 NM_001373937 RefSeq (protein) NP_000761 NP_001185782 NP_001185783 NP_001185784 NP_034133 NP_001360866 Location (UCSC) Chr 10: 95.04 – 95.07 Mb Chr 19: 39.5 – 39.56 Mb PubMed search [3] [4]
Wikidata
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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.^[6]
• Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance.^[6]
• 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.^[6]

Selected inducers, inhibitors and substrates of CYP2C8

Substrates	Inhibitors	Inducers
amodiaquine[6] (antimalarial, anti-inflammatory) cerivastatin[6] (statin) enzalutamide (antiandrogen) paclitaxel[6] (chemotherapeutic) repaglinide[6] (antidiabetic) torasemide[6] (loop diuretic) sorafenib[6] (tyrosine kinase inhibitor) rosiglitazone (antidiabetic) - converted to active metabolites[7] buprenorphine (semisynthetic opioid) polyunsaturated fatty acids montelukast (leukotriene receptor antagonist)	Strong gemfibrozil[6] (hypolipidemic) the acyl-β-glucuronide metabolite of clopidogrel[8] (antiplatelet) Moderate trimethoprim[6] (antibiotic) Unspecified potency thiazolidinediones[6] (antidiabetic) montelukast[6] (leukotriene receptor antagonist) quercetin[6] (antiinflammatory)	Unspecified potency rifampicin[6] (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).^[9][10][11]

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.^[12][13]

See also

• Cytochrome P450 oxidase
• Epoxygenase