CYP4F12

Description

The CYP4F12 (cytochrome P450 family 4 subfamily F member 12) is a protein-coding gene located on chromosome 19.

Cytochrome P450 4F12 is a protein that in humans is encoded by the CYP4F12 gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes and is part of a cluster of cytochrome P450 genes on chromosome 19. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein likely localizes to the endoplasmic reticulum. CYP4F12 is expressed in the liver and throughout the gastrointestinal track, is known to metabolize the anti-histamine drugs, ebastine and terfenadine, and therefore is suggested to be positioned for and possibly involved in the processing of these and perhaps other drugs. When expressed in yeast the enzyme is capable of oxidizing arachidonic acid by adding a hydroxyl residue to carbons 18 or 19 to form 18-hydroxyeicosatetraenoic acid (18-HETE) or 19-HETE; however, its physiological function in doing so has not been determined. CYP4F12 also metabolizes prostaglandin H2 (PGH2) and PGH1 to their corresponding 19-hydroxyl analogs in a reaction that might serve to reduce their activities. In addition to these monooxygenase actions, CYP458 possesses epoxygenase activity: it metabolizes the omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid, (EPA) to their corresponding epoxides, the epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs), respectively. The enzyme metabolizes DHA primarily to 19R,20S-epoxyeicosapentaenoic acid and 19S,20R-epoxyeicosapentaenoic acid isomers (termed 19,20-EDP) and EPA primarily to 17R,18S-eicosatetraenoic acid and 17S,18R-eicosatetraenoic acid isomers (termed 17,18-EEQ). 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule which acts to constrict arterioles, elevate blood pressure, promote inflammation responses, and stimulates the growth of various types of tumor cells; however the in vivo ability and significance of 19-HETE in inhibiting 20-HETE has not been demonstrated (see 20-Hydroxyeicosatetraenoic acid).

CYP4F12 is a cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs). It uses molecular oxygen to insert one oxygen atom into a substrate, reducing the second oxygen atom into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase. It catalyzes the hydroxylation of carbon hydrogen bonds, with a preference for the omega-2 position. CYP4F12 metabolizes arachidonate to 18-hydroxy arachidonate and catalyzes the epoxidation of double bonds of PUFAs such as docosapentaenoic and docosahexaenoic acids. It has low omega-hydroxylase activity toward leukotriene B4 and arachidonate. It is also involved in the metabolism of xenobiotics, catalyzing the hydroxylation of the antihistamine drug ebastine.

CYP4F12 is also known as CYPIVF12, F22329_1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing