CYP2C8

Cytochrome P450, family 2, subfamily C, polypeptide 8
PDB rendering based on 1pq2.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1PQ2, 2NNH, 2NNI, 2NNJ, 2VN0
Identifiers
Symbols	CYP2C8 ; CPC8; CYPIIC8; MP-12/MP-20
External IDs	OMIM: 601129 MGI: 1917138 HomoloGene: 117948 ChEMBL: 3721 GeneCards: CYP2C8 Gene
EC number	1.14.14.1
Gene ontology Molecular function • monooxygenase activity • iron ion binding • arachidonic acid epoxygenase 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 • oxygen binding • heme binding • caffeine oxidase activity • aromatase activity Cellular component • cytoplasm • endoplasmic reticulum membrane • intracellular membrane-bounded organelle Biological process • organic acid metabolic process • xenobiotic metabolic process • drug metabolic process • arachidonic acid metabolic process • epoxygenase P450 pathway • exogenous drug catabolic process • small molecule metabolic process • oxidation-reduction process • oxidative demethylation • omega-hydroxylase P450 pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1558	13095
Ensembl	ENSG00000138115	ENSMUSG00000003053
UniProt	P10632	Q64458
RefSeq (mRNA)	NM_000770	NM_007815
RefSeq (protein)	NP_000761	NP_031841
Location (UCSC)	Chr 10: 95.04 – 95.07 Mb	Chr 19: 39.27 – 39.33 Mb
PubMed search	[1]	[2]

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. metabolizes long-chain polyunsaturated fatty acids, e.g. arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid to their biologically active epoxides. For example, it metabolizes arachidonic acid to the following eicosatrienoic acid epoxides: 5,6-epoxy-8Z,11Z,14Z-eicosatetrienoic acid, 5,6-epoxy-8Z,11Z,14Z-eicosatetrienoic acid, 11,12-epoxy-5Z,8Z,14Z-eicosatetrienoic acid, and 14,15-epoxy-5Z,8Z,11Z-eicosatetrainoic acid; animal models and a limited set of human studies implicate these epoxides in reducing hypertension; protecting against the Myocardial infarction and other insults to the heart; promoting the growth and metastasis of certain cancers; inhibiting inflammation; stimulating blood vessel formation; and possessing a variety of actions on neural tissues including modulating Neurohormone release and blocking pain perception (see epoxyeicosatrienoic acid and epoxygenase pages}.

CYP2C8 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

Substrates	Inhibitors	Inducers
amodiaquine (antimalarial, anti-inflammatory) cerivastatin (statin) enzalutamide paclitaxel (chemotherapeutic) repaglinide (antidiabetic) torasemide (loop diuretic) sorafenib (tyrosine kinase inhibitor) rosiglitazone (antidiabetic) - converted to active metabolites buprenorphine polyunsaturated fatty acids	Strong: gemfibrozil (hypolipidemic) Moderate trimethoprim (antibiotic) Unspecified potency thiazolidinediones (antidiabetic) montelukast (leukotriene receptor antagonist) quercetin (antiinflammatory)	rifampicin (antibiotic)

Where classes of agents are listed, there may be exceptions within the class.

See also

• Cytochrome P450 oxidase