Cholerton S, Daly A K, Idle J R
Department of Pharmacological Sciences, University of Newcastle upon Tyne, Medical School, UK.
Trends Pharmacol Sci. 1992 Dec;13(12):434-9. doi: 10.1016/0165-6147(92)90140-2.
Recent advances in the study of human cytochromes P450 by protein purification, molecular cloning techniques and analysis of polymorphisms has led to increased understanding of the role of the various forms in the metabolism of clinically important drugs. In particular, the substrate specificity of one form, CYP2D6, is well established. CYP2D6 shows polymorphism, with 5-10% of Caucasians (poor metabolizers) not expressing this enzyme. The molecular basis of this deficiency is now well understood and methods for the detection of poor metabolizers are discussed, as well as the effect of the polymorphism on drug metabolism. Substrate specificities and possible polymorphisms in other cytochromes P450 are also discussed.
通过蛋白质纯化、分子克隆技术以及多态性分析对人类细胞色素P450开展的最新研究进展，增进了人们对各种形式的细胞色素P450在临床重要药物代谢中所起作用的理解。特别是，其中一种形式CYP2D6的底物特异性已得到充分证实。CYP2D6具有多态性，5%至10%的高加索人（代谢不良者）不表达这种酶。目前已充分了解这种缺陷的分子基础，并讨论了检测代谢不良者的方法，以及该多态性对药物代谢的影响。还讨论了其他细胞色素P450的底物特异性和可能存在的多态性。
