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CYP4A11

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).

Pathway

Lipid metabolism; arachidonate metabolism.

Lipid metabolism; oxylipin biosynthesis.

Sequence similarities

Belongs to the cytochrome P450 family.

Tissue specificity

Expressed in liver (PubMed:7679927). Expressed in S2 and S3 segments of proximal tubules in cortex and outer medulla of kidney (PubMed:7679927, PubMed:10660572).

Cellular localization

  • Endoplasmic reticulum membrane
  • Peripheral membrane protein
  • Microsome membrane
  • Peripheral membrane protein

Alternative names

  • Cytochrome P450 4A11
  • 20-hydroxyeicosatetraenoic acid synthase
  • CYP4AII
  • CYPIVA11
  • Cytochrome P-450HK-omega
  • Cytochrome P450HL-omega
  • Fatty acid omega-hydroxylase
  • Lauric acid omega-hydroxylase
  • Long-chain fatty acid omega-monooxygenase
  • 20-HETE synthase
  • CYP4A2
  • CYP4A11

Target type

Proteins

Molecular weight

59348Da