CYP4A11
CYP4A11 (Cytochrome P450 Family 4 Subfamily A Member 11) is a Protein Coding gene. Diseases associated with CYP4A11 include Generalized Atherosclerosis and Hypertensive Nephropathy. Among its related pathways are Arachidonic acid metabolism and Constitutive Androstane Receptor Pathway. Gene Ontology (GO) annotations related to this gene include iron ion binding and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. An important paralog of this gene is CYP4A22.
Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids and their oxygenated derivatives (oxylipins) (PubMed:7679927, PubMed:1739747, PubMed:8914854, PubMed:10553002, PubMed:10660572, PubMed:15611369).
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:7679927, PubMed:1739747, PubMed:8914854, PubMed:10553002, PubMed:10660572, PubMed:15611369).
Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of saturated and unsaturated fatty acids, the catalytic efficiency decreasing in the following order: dodecanoic> tetradecanoic> (9Z)-octadecenoic> (9Z,12Z)-octadecadienoic> hexadecanoic acid (PubMed:10553002, PubMed:10660572).
Acts as a major omega-hydroxylase for dodecanoic (lauric) acid in liver (PubMed:7679927, PubMed:1739747, PubMed:8914854, PubMed:15611369).
Participates in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10620324, PubMed:10660572, PubMed:15611369).
Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of fatty acids with lower efficiency (PubMed:7679927).
May contribute 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).
Omega-hydroxylates (9R,10S)-epoxy-octadecanoate stereoisomer (PubMed:15145985).
Plays a minor role in omega-oxidation of long-chain 3-hydroxy fatty acids (PubMed:18065749).
Has little activity toward prostaglandins A1 and E1 (PubMed:7679927).
Biological Process
Arachidonic acid metabolic process Source: UniProtKB
Epoxygenase P450 pathway Source: UniProtKB
Fatty acid metabolic process Source: Reactome
Icosanoid biosynthetic process Source: GO_Central
Kidney development Source: GO_Central
Lauric acid metabolic process Source: GO_Central
Leukotriene metabolic process Source: UniProtKB
Linoleic acid metabolic process Source: GO_Central
Long-chain fatty acid metabolic process Source: BHF-UCL
Omega-hydroxylase P450 pathway Source: Reactome
Oxylipin biosynthetic process Source: UniProtKB-UniPathway
Positive regulation of icosanoid secretion Source: UniProtKB
Pressure natriuresis Source: UniProtKB
Regulation of metabolic process Source: Reactome
Renal water homeostasis Source: UniProtKB
Sodium ion homeostasis Source: UniProtKB