S－美芬妥英羟化代谢多态性的分子机制研究进展  

The Molecular Mechanism of Polymorphism of S-mephenytoin Hydroxylative Metabolism

作　　者：楼雅卿[1] 匡唐永[1] 

机构地区：[1]北京医科大学药理学系

出　　处：《生理科学进展》1995年第1期23-28,共6页Progress in Physiological Sciences

摘　　要：人群中存在着Ｓ－美芬妥英羟化代谢多态性。从人肝微粒体已分离出Ｓ－美芬妥英羟化酶。在基因克隆研究中已分离出与该羟化酶活性有关的Ｐ４５０ｃＤＮＡ，属Ｐ４５０２Ｃ１９。最近报道，人肝中Ｐ４５０２Ｃ１９的含量和催活Ｓ－美芬妥英羟化活性密切相关，其弱代谢者主要由于ＣＹＰ２Ｃ１９的外显子５单碱基对（Ｇ→Ａ）的变异，使核苷酸序列错位而产生无功能的Ｐ４５０蛋白的结果。The hydroxylation of S-mephenytoin exhibits a genetic polymorphism in humans and there are a large interethnic differences in the frequency of the poor metabolizer phenotype.A S-mephenytoin P450-hydroxylase termed P4 50 UK was purified and identified to be CYP 2C 19 by amino-terminal amino acid analyses.The levels of P450 2C19 and the ability of the human liver samples to 4'-hydroxylate Smephenytoin were found to be strongly correlative.Recent report showed that the principle defect in S-mephenytoin poor metabolizers is a single base pair(G→A)mutation in exon 5 of CYP 2C 19 resulting in an aberrantly spliced mRNA and a non-functional P450 2C 19 protein in liver of S-mephenytoin PM.Further investigations demonstrate that this major defect is responsible for about 75% of poor metabolizer phenotype in both caucasians and orientals who are homozygous for S-mephenytoin hydroxylation defect.This genetic defect(CYP 2C 19)also affects metabolism of several other widely clinical used drugs.

关 键 词：S-美芬妥英 多态性 遗传变异 基因分析 

分 类 号：R968[医药卫生—药理学]