Semin Liver Dis 1998; 18(4): 331-343
DOI: 10.1055/s-2007-1007168
ORIGINAL ARTICLE

© 1998 by Thieme Medical Publishers, Inc.

Regulation of Hepatic Glutathione Synthesis

Shelly C. Lu
  • USC Liver Disease Research Center, Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California School of Medicine, Los Angeles, California
Further Information

Publication History

Publication Date:
16 April 2008 (online)

ABSTRACT

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, γ-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.