Mannervik B, Danielson U H
Department of Biochemistry, University of Uppsala, Sweden.
CRC Crit Rev Biochem. 1988;23(3):283-337. doi: 10.3109/10409238809088226.
The glutathione transferases are recognized as important catalysts in the biotransformation of xenobiotics, including drugs as well as environmental pollutants. Multiple forms exist, and numerous transferases from mammalian tissues, insects, and plants have been isolated and characterized. Enzymatic properties, reactions with antibodies, and structural characteristics have been used for classification of the glutathione transferases. The cytosolic mammalian enzymes could be grouped into three distinct classes--Alpha, Mu, and Pi; the microsomal glutathione transferase differs greatly from all the cytosolic enzymes. Members of each enzyme class have been identified in human, rat, and mouse tissues. Comparison of known primary structures of representatives of each class suggests a divergent evolution of the enzyme proteins from a common precursor. Products of oxidative metabolism such as organic hydroperoxides, epoxides, quinones, and activated alkenes are possible "natural" substrates for the glutathione transferases. Particularly noteworthy are 4-hydroxyalkenals, which are among the best substrates found. Homologous series of substrates give information about the properties of the corresponding binding site. The catalytic mechanism and the active-site topology have been probed also by use of chiral substrates. Steady-state kinetics have provided evidence for a "sequential" mechanism.
谷胱甘肽转移酶被认为是外源化合物生物转化过程中的重要催化剂，这些外源化合物包括药物以及环境污染物。谷胱甘肽转移酶存在多种形式，并且已经从哺乳动物组织、昆虫和植物中分离出许多转移酶并对其进行了表征。酶的性质、与抗体的反应以及结构特征已被用于谷胱甘肽转移酶的分类。胞质哺乳动物酶可分为三个不同的类别——α、μ和π；微粒体谷胱甘肽转移酶与所有胞质酶有很大不同。在人类、大鼠和小鼠组织中已鉴定出每个酶类别的成员。对每个类别代表的已知一级结构的比较表明，这些酶蛋白是从一个共同的前体进化而来的。氧化代谢产物，如有机氢过氧化物、环氧化物、醌和活化烯烃，可能是谷胱甘肽转移酶的“天然”底物。特别值得注意的是4-羟基烯醛，它们是已发现的最佳底物之一。同源系列的底物提供了有关相应结合位点性质的信息。还通过使用手性底物来探究催化机制和活性位点拓扑结构。稳态动力学为“顺序”机制提供了证据。
