Human Cytochrome P450 3A4, CYP3A4 ELI

A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed: 10681376, PubMed: 11093772, PubMed: 11555828, PubMed: 14559847, PubMed: 12865317, PubMed: 15373842, PubMed: 15764715, PubMed: 20702771, PubMed: 19965576, PubMed: 21490593, PubMed: 21576599).

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 (NADPH--hemoprotein reductase).

Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed: 2732228, PubMed: 14559847, PubMed: 12865317, PubMed: 15373842, PubMed: 15764715, PubMed: 21576599, PubMed: 21490593).

Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed: 11555828, PubMed: 14559847, PubMed: 12865317).

Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed: 2732228, PubMed: 15373842, PubMed: 15764715, PubMed: 22773874).

Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed: 2732228, PubMed: 15373842, PubMed: 15764715).

Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed: 21576599).

Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed: 9435160).

Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed: 19965576).

Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed: 20702771).

Plays a role in the metabolism of retinoids.

Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed: 10681376).

Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed: 11093772).

Responsible for oxidative metabolism of xenobiotics.

Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed: 11159812).

Metabolizes the majority of the administered drugs.

Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed: 10759686).

Hydroxylates antimalarial drug quinine (PubMed: 8968357).

Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed: 11695850).

Also involved in vitamin D catabolism and calcium homeostasis.

Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed: 29461981).