CYP3A4 P08684

细胞色素P450 3A4 (EC 1.14.14.1) (1,4-桉叶油素2-外-单加氧酶) (1,8-桉叶油素2-外-单加氧酶) (EC 1.14.14.56) (阿苯达唑单加氧酶(亚砜形成)) (EC 1.14.14.73) (阿苯达唑亚砜化酶) (CYPIIIA3) (CYPIIIA4) (胆固醇25-羟化酶) (细胞色素P450 3A3) (细胞色素P450 HLp) (细胞色素P450 NF-25) (细胞色素P450-PCN1) (硝苯地平氧化酶) (奎宁3-单加氧酶) (EC 1.14.14.55)

功能描述

一种细胞色素P450单加氧酶，参与甾醇、类固醇激素、类视黄醇和脂肪酸的代谢 (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599)。机制上，利用分子氧将一个氧原子插入底物，并将第二个氧原子还原为水分子，所需的一对电子由NADPH通过细胞色素P450还原酶(NADPH--血红素蛋白还原酶)提供。催化碳-氢键的羟基化 (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228)。对雌酮(E1)和17β-雌二醇(E2)形成羟基雌激素表现出高催化活性，即2-羟基E1和E2，以及C-16位D环羟基化的E1和E2 (PubMed:11555828, PubMed:12865317, PubMed:14559847)。在雄激素代谢中起作用，特别是在睾酮的氧化失活中 (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228)。将睾酮代谢为生物活性较低的2β-和6β-羟基睾酮 (PubMed:15373842, PubMed:15764715, PubMed:2732228)。参与羟基胆固醇（氧甾醇）的形成，特别是C-4β位A环羟基化胆固醇和C-25位侧链羟基化胆固醇，可能有助于胆固醇降解和胆汁酸生物合成 (PubMed:21576599)。催化多不饱和脂肪酸(PUFA)的双烯丙位羟基化 (PubMed:9435160)。催化PUFA双键的环氧化，优先作用于最后一个双键 (PubMed:19965576)。代谢内源性大麻素花生四烯酸乙醇胺（anandamide）生成8,9-、11,12-和14,15-环氧二十碳三烯酸乙醇胺(EpETrE-EAs)，可能调节内源性大麻素系统信号传导 (PubMed:20702771)。在类视黄醇代谢中起作用。对全反式视黄醇氧化为全反式视黄醛表现出高催化活性，这是全反式视黄酸(atRA)生物合成的限速步骤 (PubMed:10681376)。进一步代谢atRA生成4-羟基视黄酸，可能在肝脏atRA清除中起作用 (PubMed:11093772)。负责外源性物质的氧化代谢。作为植物脂质1,8-桉叶油素（桉油精）的2-外-单加氧酶 (PubMed:11159812)。代谢大多数给药药物。催化驱虫药阿苯达唑和芬苯达唑的亚砜化 (PubMed:10759686)。羟基化抗疟药奎宁 (PubMed:8968357)。作为1,4-桉叶油素2-外-单加氧酶 (PubMed:11695850)。也参与维生素D分解代谢和钙稳态。催化活性激素骨化三醇（1α,25-二羟基维生素D(3)）的失活 (PubMed:29461981)。 {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:10759686, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:11159812, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15373842, ECO:0000269|PubMed:15764715, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20702771, ECO:0000269|PubMed:21490593, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:22773874, ECO:0000269|PubMed:2732228, ECO:0000269|PubMed:29461981, ECO:0000269|PubMed:8968357, ECO:0000269|PubMed:9435160}.

组织特异性

Expressed in prostate and liver. According to some authors, it is not expressed in brain (PubMed:19094056). According to others, weak levels of expression are measured in some brain locations (PubMed:18545703, PubMed:19359404). Also expressed in epithelium of the small intestine and large intestine, bile duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder, intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary (at protein level).

亚细胞定位

Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane