A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, eicosanoids and vitamins (PubMed:18577768, PubMed:10833273, PubMed:10660572, PubMed:11997390, PubMed:17341693, PubMed:18574070). 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). Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of long- and very long-chain fatty acids. Displays high omega-hydroxylase activity toward polyunsaturated fatty acids (PUFAs) (PubMed:18577768). Participates in the conversion of arachidonic acid to omega-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10660572, PubMed:17341693, PubMed:18574070). Plays a role in the oxidative inactivation of eicosanoids, including both pro-inflammatory and anti-inflammatory mediators such as leukotriene B4 (LTB4), lipoxin A4 (LXA4), and several HETEs (PubMed:8026587, PubMed:9799565, PubMed:10833273, PubMed:10660572, PubMed:17341693, PubMed:18574070, PubMed:18577768). Catalyzes omega-hydroxylation of 3-hydroxy fatty acids (PubMed:18065749). Converts monoepoxides of linoleic acid leukotoxin and isoleukotoxin to omega-hydroxylated metabolites (PubMed:15145985). Contributes to the degradation of very long-chain fatty acids (VLCFAs) by catalyzing successive omega-oxidations and chain shortening (PubMed:16547005, PubMed:18182499). Plays an important role in vitamin metabolism by chain shortening. Catalyzes omega-hydroxylation of the phytyl chain of tocopherols (forms of vitamin E), with preference for gamma-tocopherols over alpha-tocopherols, thus promoting retention of alpha-tocopherols in tissues (PubMed:11997390). Omega-hydroxylates and inactivates phylloquinone (vitamin K1), and menaquinone-4 (MK-4, a form of vitamin K2), both acting as cofactors in blood coagulation (PubMed:19297519, PubMed:24138531). an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 22-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (9S,10R)-epoxy-octadecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 18-hydroxy-(9S,10R)-epoxy-octadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (9R,10S)-epoxy-octadecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 18-hydroxy-(9R,10S)-epoxy-octadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 12,13-epoxy-(9Z)-octadecenoate + O2 + reduced [NADPH--hemoprotein reductase] = 18-hydroxy-12,13-epoxy-(9Z)-octadecenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 9,10-epoxy-(12Z)-octadecenoate + O2 + reduced [NADPH--hemoprotein reductase] = 18-hydroxy-9,10-epoxy-(12Z)-octadecenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 8-hydroxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 8,20-dihydroxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 12,20-dihydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 12-hydroxyoctadecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 12,18-dihydroxyoctadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] docosanoate + O2 + reduced [NADPH--hemoprotein reductase] = 22-hydroxydocosanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 22-hydroxydocosanoate + O2 + reduced [NADPH--hemoprotein reductase] = 22-oxodocosanoate + H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase] 22-oxodocosanoate + O2 + reduced [NADPH--hemoprotein reductase] = docosanedioate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase] O2 + reduced [NADPH--hemoprotein reductase] + tetracosanoate = 24-hydroxytetracosanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] hexacosanoate + O2 + reduced [NADPH--hemoprotein reductase] = 26-hydroxyhexacosanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 26-hydroxyhexacosanoate + O2 + reduced [NADPH--hemoprotein reductase] = 26-oxohexacosanoate + H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase] 26-oxohexacosanoate + O2 + reduced [NADPH--hemoprotein reductase] = 2 H(+) + H2O + hexacosanedioate + oxidized [NADPH--hemoprotein reductase] 3-hydroxyoctadecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 3,18-dihydroxyoctadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 3-hydroxyhexadecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 3,16-dihydroxyhexadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] leukotriene B4 + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-leukotriene B4 + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 6-trans-leukotriene B4 + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-6-trans-leukotriene B4 + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] lipoxin A4 + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-lipoxin A4 + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] menaquinone-4 + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + omega-hydroxymenaquinone-4 + oxidized [NADPH--hemoprotein reductase] O2 + phylloquinone + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + omega-hydroxyphylloquinone + oxidized [NADPH--hemoprotein reductase] (+)-alpha-tocopherol + O2 + reduced [NADPH--hemoprotein reductase] = 13-hydroxy-alpha-tocopherol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] gamma-tocopherol + H(+) + NADPH + O2 = 13-hydroxy-gamma-tocopherol + H2O + NADP(+) Inhibited by dietary sesamin. kcat is 0.067 min(-1) with menaquinone-4 (MK-4) as substrate (PubMed:24138531). The omega-hydroxylation of VLCFAs follows dual-enzyme Michaelis-Menten kinetics, suggesting simultaneous binding of two substrate molecules. The high affinity Michaelis-Menten constants are shown (PubMed:16547005). Lipid metabolism; arachidonate metabolism. Lipid metabolism; leukotriene B4 degradation. Cofactor degradation; phylloquinone degradation. Liver. Also present in kidney: specifically expressed in the S2 and S3 segments of proximal tubules in cortex and outer medulla (PubMed:10660572). Disease susceptibility may be associated with variants affecting the gene represented in this entry. The variant Met-433 is associated with coumarin (the brand name of warfarin) resistance by increasing coumarin maintenance dose in patients on this anti-coagulant therapy. This is probably due to decreased activity of the phylloquinone omega-hydroxylase activity, leading to an increase in hepatic vitamin K levels that warfarin must antagonize (PubMed:24138531). Belongs to the cytochrome P450 family.