Target type: molecularfunction
Catalysis of the reaction: arachidonic acid + O2 + NADPH + H+ = 20-HETE + NADP+ + H2O. Arachidonic acid is also known as (5Z,8Z,11Z,14Z)-icosatetraenoic acid, and 20-HETE is also known as (5Z,8Z,11Z,14Z)-20-hydroxyicosa-5,8,11,14-tetraenoic acid. [KEGG_REACTION:R07041]
Arachidonic acid omega-hydroxylase activity catalyzes the hydroxylation of arachidonic acid at the omega position (carbon 20), introducing a hydroxyl group. This reaction is the first step in the biosynthesis of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is a bioactive lipid mediator involved in various physiological processes, including blood pressure regulation, vascular tone, inflammation, and cell growth. Arachidonic acid omega-hydroxylase activity is typically associated with cytochrome P450 (CYP) enzymes, specifically CYP4A and CYP4F isoforms. These enzymes are found in various tissues, including the liver, kidneys, and vascular endothelium. The hydroxylation reaction is catalyzed by the heme iron of the CYP enzyme, which interacts with molecular oxygen and the arachidonic acid substrate. This reaction requires NADPH and molecular oxygen, and it involves a complex series of steps, including the formation of an iron-oxygen intermediate, the abstraction of a hydrogen atom from the omega position of arachidonic acid, and the addition of a hydroxyl group. The overall reaction is highly specific for arachidonic acid and produces 20-HETE as the primary product. 20-HETE exerts its effects by activating or inhibiting specific downstream signaling pathways, such as the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K) pathway. The regulation of arachidonic acid omega-hydroxylase activity is critical for maintaining vascular homeostasis and modulating various physiological processes. Dysregulation of this activity has been implicated in several diseases, including hypertension, atherosclerosis, and cancer.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Cytochrome P450 2U1 | A cytochrome P450 2U1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q7Z449] | Homo sapiens (human) |
| Cytochrome P450 4A22 | A cytochrome P450 4A22 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q5TCH4] | Homo sapiens (human) |
| Cytochrome P450 4F2 | A cytochrome P450 4F2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P78329] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 17-octadecynoic acid | octadec-17-ynoic acid : An acetylenic fatty acid that is octadecanoi acid (stearic acid) which has been doubly dehydrogenated at positions 17 and 18 to give the corresponding alkynoic acid. | acetylenic fatty acid; long-chain fatty acid; monounsaturated fatty acid; terminal acetylenic compound | EC 1.14.14.94 (leukotriene-B4 20-monooxygenase) inhibitor; EC 1.14.15.3 (alkane 1-monooxygenase) inhibitor; P450 inhibitor |
| ketoconazole | 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively. | dichlorobenzene; dioxolane; ether; imidazoles; N-acylpiperazine; N-arylpiperazine | |
| tranylcypromine | (1R,2S)-tranylcypromine : A 2-phenylcyclopropan-1-amine that is the (1R,2S)-enantiomer of tranylcypromine. tranylcypromine : A racemate comprising equal amounts of (1R,2S)- and (1S,2R)-2-phenylcyclopropan-1-amine. An irreversible monoamine oxidase inhibitor that is used as an antidepressant (INN tranylcypromine). Tranylcypromine: A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311) | 2-phenylcyclopropan-1-amine | |
| proadifen hydrochloride | |||
| pirlindole | pirlindole: RN given refers to parent cpd; synonym pyrazidol refers to mono-HCl; structure in Negwer, 5th ed, #2812 | carbazoles | |
| kaf156 | ganaplacide: antimalarial |