人肝细胞色素P4502C金属酶和药物代谢.pdfVIP

21 5 化 学 进 展 Vol. 21 No. 5 2009 5 PROGRESS IN CHEMISTRY May, 2009 人肝细胞色素P450 2C金属酶与药物代谢* 蒋华麟 谭相石* * ( 复旦大学化学系生物医学研究院 上海200433) 由于人肝细胞色素P450 2C 亚家族 临床药物代谢的密切关系, 其研究已引起人们的广泛关 注本文综述了4 种人肝细胞色素P450 2C, 着重综述了其中的三种: CYP2C9, CYP2C8, CYP2C19 的研究进 展评述了CYP2C9, CYP2C8 和CYP2C19 的某些氨基酸残基在催化过程中的作用, 这三种酶的基因多态在 不同人种中的分布及药物代谢的差异, 以及它们 用药的特异性及某些疾病的易感性的联系, 介绍了目前提 出的CYP2C8 的底物药效团模型, 最后总结了CYP2C9, CYP2C8, CYP2C19, CYP2C18 的主要特性 细胞色素P450 金属酶 基因多态性 用药特异性 : Q519 : A : 1005-281X( 2009) 05-0911-08 Human Hepatic Cytochrome P450 2C Metalloenzymes and Drug Metabolism * * Jiang H ualin Tan X iang shi ( Department of Chemistry, Institute of Biomedi al S ien es, Fudan University, Shanghai 200433, China) Abstract Be ause of their lose relationship to metabolism of lini ally pres ribed drugs, human hepati yto hrome P450 2C subfamily has been paid wide attention. Resear h progress of four human hepati yto hrome P450 2Cs are reviewed in this paper. Three of them, CYP2C9, CYP2C8, CYP2C19, are espe ially fo used on. The fun tions of some of their amino a id residues, distribution in various ethni groups and differen e in metabolizing drugs of their polymorphisms, and their relationship with drug spe ifi ity and some diseases sus eptibility are reviewed. A pharma ophore model of CYP2C8 substrate is introdu ed, and main hara teristi s of CYP2C9, CYP2C8, CYP2C19, CYP2C18 are summarized. Key ords yto hromes P450; metalloenzyme; gene polymorphisms; drug usage individuation [ 1) 9]