肝损状态下尿苷二磷酸葡萄糖醛酸转移酶研究进展

Hepatic UDP-glucuronosyltransferases in liver injury

肝脏是人体内最重要的代谢器官,包含绝大部分的Ⅰ相和Ⅱ相代谢酶,在内源性和外源性物质的代谢解毒方面起着重要的作用。参与葡萄糖醛酸代谢的尿苷二磷酸葡萄糖醛酸转移酶(UGT)是Ⅱ相代谢中最重要的酶,与常见的CYP450酶相比,研究相对滞后,尤其在肝损伤状态下UGT的相关研究仍处于探索阶段。本文参考最新UGT的研究成果,综述了UGT分子生物学目前研究的概况、肝脏分布及其与肝脏疾病的关系;总结了几种不同诱因的肝损伤病理状态UGT表达和葡萄糖醛酸代谢的变化情况并且深入探讨了相关机制,旨在为药物的肝脏代谢尤其是在肝损状态下葡萄糖醛酸结合消除研究提供一定的参考依据,为肝脏疾病患者的临床合理用药提供指导。

Liver is the most important metabolic organ in human,including the vast majority of metabolic enzymes involving phaseⅠ and phaseⅡ and playing an important role on detoxification of many endogenous and exogenous substances.UDP-glucuronosyltransferases(UGT)is the most important phaseⅡ metabolic enzyme that catalize glucuronidation in human,as compared with the CYP450 enzymes,study of UGTs lags behind,especially,the state of UGTs in liver injury is still poorly understood.This review summarizes latest studies of the UGTs in gene,protein structure and function,distribution in liver and relationship with the liver disease,then we discuss the effects of several common liver injury on hepatic UGT and glucuronidation.It will provide more reliable reference in durg metabolism in liver injury and guide the clinical rational use of drugs.