Sokołowska-Jezewicz Maria, Kryczyk Agata, Dudzik Paulina, Włodek Lidia
Jagiellonian University, Medical College, Faculty of Medicine, 7 Kopernika St., 31-034 Kraków, Poland.
Postepy Biochem. 2007;53(4):374-88.
Glutathione transferases (GSTs) catalyze nucleophilic attack of glutathione on electrophilic center of the second substrate, hydrophobic in character. It leads to the formation of glutathione S-conjugates (thioethers), which are subsequently eliminated from the organism as mercapturic acids. However, in some reactions, glutathione can also fulfills the role of a cofactor, facilitating transformation of a hydrophobic substrate molecule, and released after the structure has been changed. Glutathione transferases participate in the processes of conjugation, reduction, isomerization, synthesis of sex hormones, prostaglangins and leukotrienes, degradation of aromatic compounds and signal transduction. The role of these enzymes consists principally in increasing glutathione nucleophilicity by its appropriate positioning and binding in active center, and its following activation by catalytic amino acid residues. There are also so-called ligandins, i.e. glutathione transferases which can bind hydrophobic, non-substrate ligands, thereby contributing to their sequestration. GSTs play a dominating role in detoxification of xenobiotics eliminated from the body in the form of thioethers, which however, under certain conditions, can be bioactivated in beta-liase-catalyzed reaction to form compounds capable of forming tissue adducts. Inhibition of S-transferase activity can have therapeutic significance both when thioethers are activated by beta-liase and during carcinogenesis, which is often accompanied by overexpression of GSTs.
谷胱甘肽转移酶（GSTs）催化谷胱甘肽对第二种底物亲电中心的亲核攻击，该底物具有疏水性。这会导致谷胱甘肽S-共轭物（硫醚）的形成，随后这些共轭物会以巯基尿酸的形式从生物体中排出。然而，在某些反应中，谷胱甘肽也可以起到辅助因子的作用，促进疏水底物分子的转化，并在结构改变后释放。谷胱甘肽转移酶参与共轭、还原、异构化、性激素、前列腺素和白三烯的合成、芳香化合物的降解以及信号转导过程。这些酶的作用主要在于通过在活性中心的适当定位和结合来增加谷胱甘肽的亲核性，并随后通过催化氨基酸残基对其进行激活。此外，还有所谓的配体结合蛋白，即能够结合疏水性非底物配体的谷胱甘肽转移酶，从而有助于对这些配体进行隔离。GSTs在以硫醚形式从体内清除的外源化合物的解毒过程中起主导作用，然而，在某些条件下，硫醚可以在β-裂解酶催化的反应中被生物激活，形成能够形成组织加合物的化合物。当硫醚被β-裂解酶激活以及在致癌过程中（致癌过程通常伴随着GSTs的过度表达），抑制S-转移酶活性可能具有治疗意义。
