Lu S C
USC Liver Disease Research Center, Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
Semin Liver Dis. 1998;18(4):331-43. doi: 10.1055/s-2007-1007168.
Glutathione (GSH) is one of the most important intracellular peptides, playing a multifunctional role ranging from antioxidant defense to modulation of immune function. GSH is synthesized by all mammalian cells, and the synthesis of GSH is a tightly regulated process. Two of the major determinants of GSH synthesis are the availability of cysteine, the sulfur amino acid precursor, and the activity of the rate-limiting enzyme, gamma-glutamylcysteine synthetase (GCS). In the liver, the major factors that determine the availability of cysteine are the activities of the membrane transport processes of the three sulfur amino acids--cysteine, cystine (under certain oxidative stress conditions) and methionine--and the conversion of methionine to cysteine through the trans-sulfuration pathway. Since the molecular cloning of GCS, there has been an explosion of knowledge regarding how this enzyme is regulated. Both transcriptional and posttranscriptional regulation play important roles in modulating the activity of this critical cellular enzyme.
谷胱甘肽（GSH）是最重要的细胞内肽之一，发挥着从抗氧化防御到免疫功能调节的多种功能。所有哺乳动物细胞都能合成GSH，且GSH的合成是一个受到严格调控的过程。GSH合成的两个主要决定因素是半胱氨酸（硫氨基酸前体）的可用性以及限速酶γ-谷氨酰半胱氨酸合成酶（GCS）的活性。在肝脏中，决定半胱氨酸可用性的主要因素是三种硫氨基酸（半胱氨酸、胱氨酸（在某些氧化应激条件下）和蛋氨酸）的膜转运过程的活性，以及通过转硫途径将蛋氨酸转化为半胱氨酸。自GCS的分子克隆以来，关于该酶如何被调控的知识呈爆发式增长。转录调控和转录后调控在调节这种关键细胞酶的活性中都发挥着重要作用。
