Current Status of the γ-Glutamyl Cycle

  • A. Meister
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Summary

According to the γ-Glutamyl cycle, the first step in glutathione breakdown is catalyzed by γ-Glutamyl transpeptidase, which transfers the γ-Glutamyl moiety of glutathione to an acceptor amino acid to form a γ-Glutamyl amino acid. γ-Glutamyl amino acids may be hydrolyzed, participate themselves in transpeptidation, or be converted by γ-Glutamyl cyclotransferase to 5-oxoproline and the corresponding amino acids. 5–0xoproline is converted to glutamate in a reaction coupled with ATP cleavage to ADP and inorganic phosphate. Cysteinyl-glycine, formed in the transpeptidation reaction, is split to cysteine and glycine. Glutamate, cysteine, and glycine are converted to glutathione in two successive steps catalyzed, respectively, by γ-Glutamylcysteine and glutathione synthetases. Metabolite labeling studies and experiments with specific inhibitors that block the cycle at various steps showed that the reactions of the cycle take place in vivo. Studies with enzyme inhibitors and other data, including information obtained from observations on patients with inborn blocks of the cycle, indicate that the γ-Glutamyl cycle accounts for the turnover of intracellular glutathione and functions as one of the systems that mediates translocation of amino acids. Recent in vivo studies on the effect of amino acid administration on glutathione and 5-oxoproline levels, and on the effects of specific inhibition of glutathione synthesis and γ-Glutamyl transpeptidase indicate that there is a physiologically significant connection between the metabolism of glutathione and amino acid transport.

Keywords

Cysteine Proline Methionine Tate Homocysteine 

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  • A. Meister

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