CYP4F2

Function

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, fatty acids, and other lipids. This protein localizes to the endoplasmic reticulum. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F11, is approximately 16 kb away.

CYP4F2 along with CYP4A22, CYP4A11, and CYP4F3 and CYP2U1 also metabolize arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) by an Omega oxidation reaction with the predominant 20-HETE-synthesizing enzymes in humans being CYP4F2 followed by CYP4A11; 20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans. Gene polymorphism variants of CYP4F2 are associated with the development of hypertension, cerebral infarction (i.e. ischemic stroke), and myocardial infarction in humans (see 20-Hydroxyeicosatetraenoic acid for details).,

Members of the CYP4A and CYP4F sub-families may also ω-hydroxylate and thereby reduce the activity of various fatty acid metabolites of arachidonic acid including LTB4, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several prostaglandins that are involved in regulating various inflammatory, vascular, and other responses in animals and humans. This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 single nucleotide variants (RSPs) with human Krohn's disease (RSPs termed Rs2108622 and Coeliac disease (rs3093156 and rs3093156).