CYP4F3
This gene, CYP4F3, 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. 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, CYP4F8, is approximately 18 kb away. [provided by RefSeq]
Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins) (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15145985, PubMed:16547005, PubMed:16820285, PubMed:18182499, PubMed:18065749, PubMed:18577768).
Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:9675028).
May play a role in inactivation of proinflammatory and anti-inflammatory oxylipins during the resolution of inflammation (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15145985, PubMed:15364545, PubMed:16547005, PubMed:16820285, PubMed:18182499, PubMed:18065749, PubMed:18577768).
Isoform CYP4F3A:
Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of oxylipins in myeloid cells, displaying higher affinity for arachidonate metabolite leukotriene B4 (LTB4) (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15364545).
Inactivates LTB4 via three successive oxidative transformations to 20-hydroxy-LTB4, then to 20-oxo-LTB4 and to 20-carboxy-LTB4 (PubMed:9675028).
Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate (PubMed:15145985).
Omega-hydroxylates monohydroxy polyunsaturated fatty acids (PUFAs), including hydroxyeicosatetraenoates (HETEs) and hydroxyeicosapentaenoates (HEPEs), to dihydroxy compounds (PubMed:15364545, PubMed:9675028).
Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acid, thereby initiating chain shortening (PubMed:18182499).
Has low hydroxylase activity toward PUFAs (PubMed:18577768, PubMed:11461919).
Isoform CYP4F3B:
Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of polyunsaturated fatty acids (PUFAs) (PubMed:11461919, PubMed:16820285, PubMed:18577768).
Participates in the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:11461919, PubMed:16820285, PubMed:18577768).
Has high omega-hydroxylase activity toward other PUFAs, including eicosatrienoic acid (ETA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (PubMed:16820285, PubMed:18577768).
Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of PUFAs with lower efficiency (PubMed:18577768).
Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid and hexacosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acids, thereby initiating chain shortening (PubMed:16547005, PubMed:18182499).
Omega-hydroxylates long-chain 3-hydroxy fatty acids, likely initiating the oxidative conversion to the corresponding 3-hydroxydicarboxylic fatty acids (PubMed:18065749).
Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate (PubMed:15145985).
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