Vincenzini M T, Favilli F, Stio M, Iantomasi T
Department of Biochemical Sciences, University of Florence, Italy.
Biochim Biophys Acta. 1991 Apr 9;1073(3):571-9. doi: 10.1016/0304-4165(91)90232-6.
The epithelium of the small intestine act by the formation of GSH-S-conjugation, as a first line of defence against various ingested toxic chemicals. GSH and GSH-dependent enzymes are present in the gastrointestinal wall. We and others have characterized the GSH-specific transport systems in intestinal brush-border and in basolateral membrane vesicles, in which gamma-glutamyltranspeptidase (gamma-GT) activity was inactivated by AT-125. In the present study we use inhibition experiments, kinetic studies, trans-stimulation of GSH uptake and HPLC determination to demonstrate (for the first time) that GSH and two GSH-S-conjugates (chosen as model compounds) share a common transport system. Plasma GSH-S-conjugates that may enter the intestinal cells via basolateral membrane, and GSH-S-conjugates that form in intestinal cells, may be eliminated directly by this GSH transporter across brush-border membranes or transported into lumen to the active site of gamma-GT; they are then further metabolized and excreted by various routes. This transport system may thus contribute to the intestinal detoxication role.
小肠上皮通过形成谷胱甘肽-S-结合物发挥作用，作为抵御各种摄入的有毒化学物质的第一道防线。谷胱甘肽（GSH）和依赖GSH的酶存在于胃肠道壁中。我们和其他人已经对肠道刷状缘和基底外侧膜囊泡中的GSH特异性转运系统进行了表征，其中γ-谷氨酰转肽酶（γ-GT）活性被AT-125灭活。在本研究中，我们使用抑制实验、动力学研究、GSH摄取的转刺激和高效液相色谱测定法（首次）证明GSH和两种GSH-S-结合物（作为模型化合物选择）共享一个共同的转运系统。可能通过基底外侧膜进入肠细胞的血浆GSH-S-结合物，以及在肠细胞中形成的GSH-S-结合物，可能通过这种GSH转运体直接穿过刷状缘膜消除，或转运到肠腔至γ-GT的活性位点；然后它们通过各种途径进一步代谢和排泄。因此，这个转运系统可能有助于肠道的解毒作用。
