Armstrong R N
Department of Chemistry and Biochemistry, University of Maryland, College Park.
CRC Crit Rev Biochem. 1987;22(1):39-88. doi: 10.3109/10409238709082547.
Enzyme catalyzed detoxication reactions are one of the primary defenses organisms have against chemical insult. This article reviews current chemical approaches to understanding the cooperative role of enzymes in the metabolism of foreign compounds. Emphasis is placed on chemical and stereochemical studies which help elucidate the mechanism of action and active-site topologies of the detoxication enzymes. The stereoselectivity of the cytochromes P-450 and flavin containing monooxygenases as well as the role of hemoglobin and lipid peroxidation in the primary metabolism of xenobiotics is discussed. Current knowledge of the mechanism and stereoselectivity of epoxide hydrolase is also presented. Three enzymes involved in secondary metabolism of xenobiotics, UDP-glucuronosyltransferase, sulfotransferase and glutathione S-transferase are discussed with particular emphasis on active site topology and cooperative participation with the enzymes of primary metabolism.
酶催化解毒反应是生物体抵御化学损伤的主要防御机制之一。本文综述了当前用于理解酶在异源化合物代谢中协同作用的化学方法。重点是化学和立体化学研究，这些研究有助于阐明解毒酶的作用机制和活性位点拓扑结构。讨论了细胞色素P-450和含黄素单加氧酶的立体选择性，以及血红蛋白和脂质过氧化在异源生物初级代谢中的作用。还介绍了目前关于环氧水解酶机制和立体选择性的知识。讨论了参与异源生物次级代谢的三种酶，尿苷二磷酸葡萄糖醛酸基转移酶、磺基转移酶和谷胱甘肽S-转移酶，特别强调了活性位点拓扑结构以及与初级代谢酶的协同参与。
