细胞色素P450 CYP2E1酶构型特征及其表达调控机制的研究进展

细胞色素P450CYP2E1酶参与代谢活化及失活多种前毒物、前致癌物和少数药物。在细胞色素P450超家族中,CYP2E1具有易介导自由基生成引发氧化应激反应的特征。CYP2E1表达水平可能是机体对环境和工业毒物或致癌物敏感程度的重要因素。研究表明,CYP2E1可被多种内、外源性物质所调控,并且CYP2E1的药理和毒理学功能与其以蛋白构型为基础的代谢行为密切相关。本文综述了CYP2E1基因多态性、酶构型特征与其代谢活性间的关系,并分析了其区别于其他细胞色素P450亚型的表达调控机制。

Progress of research on characteristics of cytochrome P-450 CYP2E1 in protein structure and regulation mechanisms

Cytochrome P-450 CYP2E1 plays a central role in the biotransformation of a large number of small molecular weight compounds (eg drugs, toxins and pre-carcinogens). CYP2E1 can produce reactive oxygen species directly through high oxidative activity and/or through metabolism of xenobiotics. CYP2E1 levels may be associated with human susceptibility to toxicity and carcinogenicity of industrial and environmental chemicals. CYP2E1 levels can be regulated by endogenous and exogenous substrates. The roles of CYP2E1 in toxicology and pharmacology are related to the metabolic features of CYP2E1 based on the protein structure. The present review briefly discusses the advances in CYP2E1 genetic polymorphisms, protein structure-activity relationships and regulation mechanisms compared with other CYP isoforms.