CYP4F8

Description

The CYP4F8 (cytochrome P450 family 4 subfamily F member 8) is a protein-coding gene located on chromosome 19.

Cytochrome P450 4F8 is a protein that in humans is encoded by the CYP4F8 gene. 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 and other lipids. This protein localizes to the endoplasmic reticulum and functions as a 19-hydroxylase of the arachidonic acid metabolite, prostaglandin H2 (PGH2) and the Dihomo-γ-linolenic acid metabolite PGH1 in seminal vesicles. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F3, is approximately 18 kb away. In addition to seminal vesicles, CYP4F8 is expressed in kidney, prostate, epidermis, and corneal epithelium, and its mRNA has been found in retina; CYP4F8 is also greatly up-regulated in psoriatic skin. In addition to its ability to metabolize and presumably thereby to inactivate or reduce the activity of PGH2 and PGH1, CYP4F8 adds hydroxyl residues to carbons 18 and 19 of arachidonic acid and Dihomo-γ-linolenic acid, CYP458 possesses epoxygenase activity in that 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).

CYP4F8 is a cytochrome P450 monooxygenase that metabolizes polyunsaturated fatty acids (PUFAs) and their oxygenated derivatives (oxylipins). It uses molecular oxygen to insert one oxygen atom into a substrate and reduce the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase. CYP4F8 preferentially hydroxylates carbon-hydrogen bonds at the omega-1 and omega-2 positions. It primarily hydroxylates arachidonate at the omega-2 position to form 18R-hydroxyeicosatetraenoic acid (18R-HETE). CYP4F8 also exhibits omega-1 hydroxylase activity towards prostaglandin H1, PGH2, and PGI2. It catalyzes the epoxidation of double bonds in PUFAs, including docosahexaenoic and docosapentaenoic acids. CYP4F8 has limited activity against PGD2, PGE1, PGE2, PGF2alpha, and leukotriene B4.

CYP4F8 is also known as CPF8, CYPIVF8.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing