title: Gamma-glutamyl-glutathione. Natural occurrence and enzymology.
abstract: The natural occurrence of gamma-glutamyl-glutathione (gamma-glutamyl-gamma-glutamylcysteinylglycine) in bile was established by analytical and chromatographic studies on the isolated and chemically synthesized materials. Evidence that it is formed in kidney was obtained. The origin of gamma-glutamyl-glutathione was explored through studies on the interaction of glutathione with gamma-glutamyl transpeptidase. When purified gamma-glutamyl transpeptidase was incubated with various concentrations (4 microM-50 mM) of glutathione, the initial rates of formation of gamma-glutamyl-glutathione were substantial at all concentrations of glutathione studied and were greater than the rates of formation of glutamate at physiological levels of glutathione (1-10 mM). The findings indicate that gamma-glutamyl transpeptidase catalyzes transpeptidation in vivo. That gamma-glutamyl-glutathione is formed in vivo and that it is a significant product of the reaction between glutathione and gamma-glutamyl transpeptidase under physiological conditions suggest that this polyanionic tetrapeptide may have a physiological role. gamma-Glutamyl-glutathione is not a substrate of glutathione reductase or of glutathione S-transferase, but it is a substrate of gamma-glutamyl-cyclotransferase. That gamma-glutamyl-glutathione has an additional negative charge as compared to glutathione suggests that it may be more effective than glutathione in forming complexes with certain metal ions and other cations.
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D006868:Hydrolysis; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D005722:gamma-Glutamylcyclotransferase / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: C050159:gamma-glutamyl-glutathione; D000217:Acyltransferases; D005723:gamma-Glutamyltransferase; D005722:gamma-Glutamylcyclotransferase; D005978:Glutathione