细胞色素P450酶催化反应动力学研究进展

Recent progresses in cytochrome P450-catalyzed reaction mechanisms

细胞色素P450是内质网膜上混合功能氧化酶系统的末端氧化酶,在生物体内分布广泛,主要催化机体内源和外源性物质在体内的氧化反应。细胞色素P450种类的多样性、催化反应类型的多样性以及底物的广谱性使其成为自然界最具催化作用的生物催化剂。在临床药物的生物学转化中,它参与大部分药物的生物氧化,因此具有重要的生物学意义。本文主要对细胞色素P450的催化反应机理,尤其是细胞色素P45催化下乙醇氧化的反应机理,及其在药代动力学方面的研究进行了综述。

Being the terminal oxidase component of mixed function oxidase system in the membrane of endoplasmic reticulum, cytochrome P450 （CYP450） has been found in all living organisms and can catalyze the oxidation of a variety of endogenous and xenobiotic compounds. Owing to the multiplicity of isoforms, substrates and catalytic mechanisms, CYP450 is considered to be among the most versatile biocatalysts known. In pharmaceutical metabolism, CYP450 is capable of catalyzing the oxidation of most pharmaceuticals and therefore has very important biological significance. This article reviewed the mechanistic explorations on CYP450- catalyzed reactions, especially the recent investigations on the mechanism of ethanol oxidation catalyzed by CYP450, as well as those in CYP450 drug metabolism.