Glutathione: interorgan translocation, turnover, and metabolism.

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Abstract
Glutathione is translocated out of cells; cells that have membrane-bound .gamma.-glutamyl transpeptidase can utilize translocated glutathione, whereas glutathione exported from cells that do not have appreciable transpeptidase enters the blood plasma. Glutathione removed from the plasma by the kidney and other organs that have transpeptidase. Studies in which mice and rats were treated with buthionine sulfoximine, a selective and potent inhibitor of .gamma.-glutamylcysteine synthetase and of glutathione synthesis, showed that glutathione turns over at a significant rate in many tissues, especially kidney, liver and pancreas; rate of turnover in mouse skeletal muscle is about 60% of that in the kidney. Experiments on rats surgically deprived of 1 or both kidneys and treated with the .gamma.-glutamyl transpeptidase inhibitor D-.gamma.-glutamyl-(o-carboxy)phenylhydrazide established that extrarenal .gamma.-glutamyl transpeptidase activity accounted for the utilization of about 1/3 of the total blood plasma glutathione. Normal animals treated with the transpeptidase inhibitor excreted large amounts of glutathione in their urine. They also excreted .gamma.-glutamylcysteine, suggesting that cleavage of glutathione at the cysteinylglycine bound may be of metabolic significance. Present and earlier findings lead to a tentative scheme (presented here) for metabolism and translocation of glutathione, .gamma.-glutamyl amino acids and related compounds.