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

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Abstract
The function of the .gamma.-glutamyl cycle was explored 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.