CYP2C19 gene

CYP2C19 (cytochrome P450 family 2, subfamily C, member 19) is a protein-coding gene located on chromosome 10q23.33. The gene is located in a cluster of cytochrome P450 genes on chromosome 10q24. An important paralog of this gene is CYP2C9.

The CYP2C19 gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene is located in the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsant mephenytoin, omeprazole, diazepam and some barbiturates.

Polymorphisms within this gene are associated with a different ability to metabolize mephenytoin, known as the "poor metabolizer" and "extensive metabolizer" phenotypes.

A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (Fer M et al. 2008). Mechanistically utilizes molecular oxygen by inserting one oxygen atom into a substrate and reducing the second into a water molecule, providing two electrons from NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (Fer M et al. 2008). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (Fer M et al. 2008). Catalyzes the epoxidation of double bonds of PUFA (Lucas D et al. 2010). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (Miyazawa M et al. 2002). CYP2C19 is responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4'-position.

1. Fer M et al. (2008) Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism. J Lipid Res 49:2379-2389
2. Lucas D et al. (2010) Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J Lipid Res 51:1125-1133
3. Miyazawa M et al. (2002) Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos 30:602-607.