葡萄糖醛酸轭合反应及其在药物代谢转化中的作用  

The Roles of Glucuronidation in Drug Metabolism

作　　者：史雪岩[1] 

机构地区：[1]中国农业大学农学与生物技术学院,北京100193

出　　处：《科技导报》2010年第4期101-109,共9页Science & Technology Review

基　　金：国家自然科学基金项目(30771426);教育部“新世纪优秀人才支持计划”项目(NCET-06-0113)

摘　　要：综述了葡萄糖醛酸轭合反应在药物代谢转化中的作用研究进展。论述了催化药物葡萄糖醛酸轭合反应的葡萄糖醛酸转移酶(UDP-Glucuronosyltransferases,UGTs)的分布、分类及其底物多样性,药物葡萄糖醛酸轭合反应的产物类型,药物葡萄糖醛酸轭合反应的毒理药理效应等;阐述了药物代谢中的去葡萄糖醛酸轭合反应的风险和意义,脑部葡萄糖醛酸转移酶的分布活性及功能,葡萄糖醛酸轭合产物的分析方法,葡萄糖醛酸轭合反应过程的个体差异、种间差异等。研究表明,葡萄糖醛酸轭合反应是重要的药物清除与代谢反应,与药物代谢、药效、毒副作用及癌症的发生等关系密切。Glucuronidation as a major phase II reaction plays important roles in biotransformation, metabolism and disposition of drugs, such as nicotine, morphine, and Tamoxifen used for curing breast cancer. This paper reviews the recent research development in drug glucuronidation. The tissue distribution, polymorphism, and substrate diversity of UDP-Glucuronosyhransferases （UGTs） for glucuronidation, products of drug glcuronidation, and pharmacology and toxicology of glucuronidation for drug metabolism are discussed, together with the risks of de-glucuronidation, the distribution and significances of UGTs in brain, the individual differences, species differences of drug glucuronidation, the analysis methods for drug glucuronides, and different research results obtained for drug glucuronidation. This review will provide some food for thought in understanding the recent developments of glucuronidation in drug disposition and metabolism, and it will be useful for further researches on the drug glucuronidation and metabolism, efficacy and toxic side effects of drugs, and the relation between drug glucuronidation and the occurrence of cancers. It is important not only to understand the roles of glucuronidation in drug metabolism, but also to develop new drugs with high efficacy, quick metabolism, and small risk of side toxic effects.

关 键 词：葡萄糖醛酸轭合反应 葡萄糖醛酸转移酶 药物代谢 

分 类 号：R914[医药卫生—药物化学]