Dierickx P J
Pharmacol Res Commun. 1984 Feb;16(2):135-43. doi: 10.1016/s0031-6989(84)80088-0.
The in vitro interaction of dithiocarb (DTC) with rat liver glutathione S-transferase was studied, using reduced glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB) as substrates. The inhibition of the GST activity by DTC was dose dependent, but not linear. The different GST isoenzymes were inhibited to different degrees. Kinetic studies revealed uncompetitive inhibition towards GSH for GST AA, and an intermediate kinetic pattern between uncompetitive and noncompetitive inhibition for the other GST isoenzymes. With respect to CDNB, mixed type inhibition was found for most GST isoenzymes, and nearly uncompetitive inhibition for GST AA and M. Titration of remaining GSH in appropriate incubation mixtures with DTC revealed no GST catalyzed conjugation of DTC with GSH. It is concluded that DTC interact with GST by direct binding to these proteins. This binding could have a protective function against DTC.
使用还原型谷胱甘肽（GSH）和1-氯-2,4-二硝基苯（CDNB）作为底物，研究了二硫代氨基甲酸盐（DTC）与大鼠肝脏谷胱甘肽S-转移酶的体外相互作用。DTC对GST活性的抑制呈剂量依赖性，但并非线性关系。不同的GST同工酶受到的抑制程度不同。动力学研究表明，GST AA对GSH表现为非竞争性抑制，而其他GST同工酶的动力学模式介于非竞争性抑制和竞争性抑制之间。对于CDNB，大多数GST同工酶表现为混合型抑制，而GST AA和M则表现为近乎非竞争性抑制。用DTC滴定适当孵育混合物中剩余的GSH，结果显示没有GST催化DTC与GSH的结合。结论是，DTC通过直接与这些蛋白质结合而与GST相互作用。这种结合可能对DTC具有保护作用。
