摘要
为了解药物ＩＩ相代谢中各酶系的最新研究进展及其临床意义。方法：按药物ＩＩ相代谢的类型分别总结了各酶系的功能、基因超家族和底物等的最新研究进展及临床意义。结果与结论：在人体内有多种类型的结合反应和大量的结合反应酶。葡醛酸结合反应是含羟基等官能团的化合物在葡醛酸转移酶（ＵＧＴ）催化下生成水溶性的Ｂ－Ｄ－葡萄糖醛酸甙，分泌到尿或胆汁中。目前已至少鉴定了１８种人类ＵＧＴ的同工酶。Ｎ－葡醛酸结合反应及其临床意义正受到广泛重视。硫酸化反应是一种重要的结合反应，转磺酶（ＳＴ）是一个基因超家族，包括酚转磺酶、雌激素转磺酶、羟基类固醇转磺酶以及脱水表雄甾酮转磺酶等。ＳＴ酶在人类中具有功能上显著的基因多态性。Ｎ－乙酰化反应在人类由具多态性的ＮＡＴ１和ＮＡＴ２催化，能修饰许多蛋白质，调节许多生理功能，ＮＡＴ的多态性与个体的癌症尤其相关。谷胱甘肽结合反应具有解毒作用，催化谷胱甘肽结合反应的酶为谷胱甘肽－Ｓ－转移酶，包括α，μ，π，θ等亚族，通过测定同工酶表达的类型和底物专属性可以研究ＧＳＴｓ在耐药性上的复杂作用。此外还有甲基化反应、氨基酸结合反应、脂肪酸结合反应、缩会反应等，在ＩＩ相代谢中发挥着各种作用。
OBJECTIVE: To review the latest progresses in research of drug phase II metabolisms and their conjugation enzymes. METHOD: The enzyme functions, gene superfamily and substrates were summarized according to the conjugation reactions types. RESULTS AND CONCLUSIONS: Phase II metabolism in the body consists of various conjugation reactions. UDP-glucuronosyltransferases (UGT) catalyze the transfer of glucuronic acid from UDP-glucuronic acid to a wide variety of endogenous and exogenous substrates which have functions such as hydroxy etc. To date at least 18 UGT isoforms have been characterized. N-glucuronidation and its clinical importance was realized extensively. Sulfation is an important conjugation reaction which is catalyzed by sulfotransferase superfamily that includes Phenol sulfotransferase, estrogen sulfotransferase, hydroxysteroid sulfotransferase and dehydroepiandrosterone sulfotransferase. Sulfotransferases have obvious polymorphism. N-acetylations are catalyzed by Nacetyltransferases (NAT1 and NAT2) which are polymorphic. N-acetylation modifies many proteins and adjusts various physiological functions. The polymorphism of NAT is particularly related to cancer diseases. Glutathione conjugation was catalyzed by glutathione S-transferases (GSTs) which have a, B, u, 0 and n- isoform etc. GSTs show complicated effects to drug-resistant by the expression of different isoforms and with various substrate specificities. Other conjugation reactions include methylations, amino acid conjugations, fatty acid conjugations and condensation reactions which play different roles in phase II metabolism.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2000年第6期458-465,共8页
The Chinese Journal of Clinical Pharmacology
关键词
药物代谢
Ⅱ相代谢
酶系
drug metabolism
phase II reaction
enzyme
