Cytochrome P450 2C8

Function

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond. Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form. Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol).

Classification

Family (Pfam)

PF00067 p450

InterPro

Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf, Cytochrome_P450_fam2

Functional cluster

Cytochrome P450 & Heme Enzymes

Experimental structures · PDB · 5

• 1PQ2 X-ray 2.70A
• 2NNH X-ray 2.60A
• 2NNI X-ray 2.80A
• 2NNJ X-ray 2.28A
• 2VN0 X-ray 2.70A

A predicted model is available from AlphaFold.

Gene Ontology · 23

• GO:0005737 cytoplasm
• GO:0005789 endoplasmic reticulum membrane
• GO:0008392 arachidonate epoxygenase activity
• GO:0034875 caffeine oxidase activity
• GO:0101020 estrogen 16-alpha-hydroxylase activity
• GO:0020037 heme binding
• GO:0005506 iron ion binding
• GO:0004497 monooxygenase activity
• GO:0016712 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
• GO:0008401 retinoic acid 4-hydroxylase activity
• GO:0019373 epoxygenase P450 pathway
• GO:0008210 estrogen metabolic process
• GO:0046456 icosanoid biosynthetic process
• GO:0002933 lipid hydroxylation
• GO:0042759 long-chain fatty acid biosynthetic process
• GO:0097267 omega-hydroxylase P450 pathway
• GO:0006082 organic acid metabolic process
• GO:0070989 oxidative demethylation
• GO:0042573 retinoic acid metabolic process
• GO:0042572 retinol metabolic process
• GO:0008202 steroid metabolic process
• GO:0042178 xenobiotic catabolic process
• GO:0006805 xenobiotic metabolic process

Disease associations

• OMIM:618018 RAW:OMIM_618018

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Cytochrome P450 2C20 0.99
• Cytochrome P450 2C38 0.99
• Cytochrome P450 2C25 0.98
• Cytochrome P450 2C29 0.98
• Cytochrome P450 2C14 0.98
• Cytochrome P450 2C28 0.98
• Cytochrome P450 2C19 0.98
• Cytochrome P450 2C6 0.98
• Cytochrome P450 2C26 0.98
• Cytochrome P450 2C7 0.98
• Cytochrome P450 2C39 0.98
• Cytochrome P450 2C50 0.98

Co-cited proteins · studied together in the literature

• Cytochrome P450 2C9 6 shared papers
• Cytochrome P450 2C18 2 shared papers
• Cytochrome P450 3A7 2 shared papers
• Cytochrome P450 2C19 3 shared papers
• Cytochrome P450 2C23 1 shared papers
• Cytochrome P450 3A4 4 shared papers
• Cytochrome P450 2C11 1 shared papers
• Cytochrome P450 1A1 3 shared papers
• Cytochrome P450 3A5 2 shared papers
• Cytochrome P450 2J2 1 shared papers
• Cytochrome P450 2D6 2 shared papers
• Cytochrome P450 1A2 2 shared papers

Literature · 23 cited papers

• Functional characterization of 12 allelic variants of CYP2C8 by assessment of paclitaxel 6alpha-hydroxylation and amodiaquine N-deethylation. Drug Metab. Pharmacokinet. · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. · 2010
• Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J. Biol. Chem. · 2008
• Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C subfamily. Biochem. Biophys. Res. Commun. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics · 2004
• A frameshift variant of CYP2C8 was identified in a patient who suffered from rhabdomyolysis after administration of cerivastatin. J. Hum. Genet. · 2004
• The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J. Biol. Chem. · 2004
• Human cytochrome P450 3A7 has a distinct high catalytic activity for the 16alpha-hydroxylation of estrone but not 17beta-estradiol. Cancer Res. · 2003
• … and 11 more in the literature graph