Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Biofactors. 2009 Nov-Dec;35(6):500-8. doi: 10.1002/biof.65.
Glutathione (GSH) is an endogenous tripeptide composed of the amino acids L-glutamate, L-cysteine, and glycine. It is found in virtually all aerobic cells and plays critical roles in maintenance of cellular redox homeostasis and drug metabolism. An important component of its regulation is transport across biological membranes. Because GSH is a charged, hydrophilic molecule, transport occurs via catalysis by specific carrier proteins rather than by simple diffusion. Although it has been clearly understood that efflux of GSH across membranes such as the canalicular and sinusoidal plasma membranes in hepatocytes and the brush-border plasma membrane in renal proximal tubules is a key step in GSH turnover and interorgan metabolism, the existence and physiological functions of uptake of GSH across various epithelial plasma membranes has been subject to some debate. Besides transport across plasma membranes, GSH transport across intracellular membranes, most notably the mitochondrial inner membrane, has received some attention in recent years because of the importance of mitochondrial redox status and the mitochondrial GSH pool in cellular physiology and pathology. This commentary will focus on renal transport processes for GSH and will discuss some of the controversies that have existed and still seem to exist in the literature, specifically regarding uptake of intact GSH by basolateral membranes of renal proximal tubular cells and uptake of intact GSH by the mitochondrial inner membrane.
谷胱甘肽（GSH）是一种内源性三肽，由氨基酸 L-谷氨酸、L-半胱氨酸和甘氨酸组成。它几乎存在于所有需氧细胞中，在维持细胞氧化还原稳态和药物代谢中起着关键作用。其调节的一个重要组成部分是穿过生物膜的转运。由于 GSH 是带电荷的亲水分子，因此通过特定载体蛋白的催化而不是简单扩散进行转运。尽管人们已经清楚地认识到，GSH 从胆管和窦状血浆膜（肝细胞）和肾近端小管的刷状缘血浆膜等膜的流出是 GSH 周转和器官间代谢的关键步骤，但 GSH 穿过各种上皮质膜的摄取的存在和生理功能仍存在一些争议。除了穿过质膜的转运外，GSH 穿过细胞内膜，特别是线粒体内膜的转运，近年来也受到了一些关注，因为线粒体氧化还原状态和线粒体 GSH 池在细胞生理学和病理学中的重要性。本评论将重点介绍 GSH 的肾转运过程，并将讨论一些在文献中仍然存在的争议，特别是关于肾近端小管细胞基底外侧膜对完整 GSH 的摄取以及完整 GSH 对线粒体内膜的摄取。
