Glutathione Turnover in the Kidney; Considerations Relating to the γ-Glutamyl Cycle and the Transport of Amino Acids

Abstract

The overall turnover of glutathione in kidney and liver was determined in studies in which L-[(14)C]glutamate was administered to mice. Turnover was much more rapid (about 5 times greater) in kidney than in liver. Studies were also carried out in which 5-oxo-L-[(14)C]proline was administered; the first order rate constants for glutathione synthesis from 5-oxoproline in liver and kidney were not far from those found for synthesis of glutathione from glutamate in these tissues. The findings are in accord with the fact that the activities of the enzymes of the gamma-glutamyl cycle are much higher in kidney than in liver. The findings of high turnover of glutathione in kidney and the rapid utilization of 5-oxoproline by this organ for glutathione synthesis are consistent with the function of the gamma-glutamyl cycle in vivo and the proposed role of gamma-glutamyl derivatives in amino-acid transport.