CYP2C9
CYP2C9 (cytochrome P450 family 2 subfamily C member 9, also known as P450IIC9 and CYP2C10) is an endoplasmic reticulum monooxygenase of the cytochrome P450 superfamily. It metabolises fatty acids, steroids and many xenobiotics, including several widely used drugs. Browse Assay Genie's current range of CYP2C9 research reagents below, or read on for the biology behind the target.
CYP2C9 is a cytochrome P450 monooxygenase involved in the metabolism of endogenous substrates such as fatty acids and steroids. Mechanistically, it uses molecular oxygen, inserting one oxygen atom into the substrate and reducing the second to water, with two electrons supplied by NADPH through cytochrome P450 reductase (NADPH--hemoprotein reductase). It catalyses the hydroxylation of carbon-hydrogen bonds and the epoxidation of double bonds in polyunsaturated fatty acids (PUFA), and also performs bisallylic hydroxylation and hydroxylation with double-bond migration of PUFA.
The enzyme metabolises cholesterol towards 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. It shows low catalytic activity in forming catechol oestrogens (2-hydroxy E1 and E2) from 17beta-estradiol and estrone. It also oxygenates the plant monoterpene limonene, (R)- and (S)-forms, to carveol and perillyl alcohol. The CYP2C9 protein localises to the endoplasmic reticulum membrane and microsomes, and its expression is induced by rifampin.
CYP2C9 contributes to the wide pharmacokinetic variability seen with drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan; ibuprofen is also among its xenobiotic substrates. Studies of individuals who are poor metabolisers of phenytoin and tolbutamide indicate that the CYP2C9 gene is polymorphic. HGNC places it in the cytochrome P450 family 2 group, within a cluster of cytochrome P450 genes on chromosome 10q. Earlier names include cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 9.
CYP2C9 metabolises many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin, making it central to drug metabolism research.
The gene is polymorphic, and poor metabolisers of phenytoin and tolbutamide have been identified, explaining part of the pharmacokinetic variability between individuals.
The enzyme epoxidises and hydroxylates polyunsaturated fatty acids, linking it to lipid metabolism and the synthesis of lipid derivatives.
CYP2C9 converts cholesterol towards 25-hydroxycholesterol, a regulator of cellular cholesterol homeostasis, and has low activity towards oestrogens.
CYP2C9 is a cytochrome P450 monooxygenase that inserts one oxygen atom into substrates using NADPH-derived electrons from cytochrome P450 reductase. It acts on fatty acids, steroids, cholesterol and many drugs, including S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
CYP2C9 is also called P450IIC9, and CYP2C10 is a previous symbol. Earlier names include cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 9. UniProt lists the protein as cytochrome P450 2C9, and its enzyme classification is EC 1.14.14.1.
Yes. CYP2C9 contributes to wide pharmacokinetic variability in the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan. Poor metabolisers of phenytoin and tolbutamide have been identified, indicating that the gene is polymorphic. Check the datasheet of any product for its validated reactivity.
Other CYP2C subfamily members, drug-metabolising cytochrome P450 enzymes and steroid-metabolising P450s with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P11712; product specifications from Assay Genie datasheets.