Evidence that the gamma-glutamyl cycle functions in vivo using intracellular glutathione: effects of amino acids and selective inhibition of enzymes.

The function of the gamma-glutamyl cycle was explored in in vivo studies in which amino acids and specific inhibitors of cycle enzymes (gamma-glutamyl transpeptidase, gamma-glutamyl cyclotransferase, gamma-glutamylcysteine synthetase, and 5-oxoprolinase) were administered to mice. The findings, which show that the gamma-glutamyl cycle functions in vivo, support the conclusion that gamma-glutamyl amino acids formed by gamma-glutamyl transpeptidase from externally supplied amino acids and intracellular glutathione are translocated into the cell and thus indicate that there is a significant physiological connection between the metabolism of glutathione and the transport of amino acids.