On the role of gamma-glutamyltransferase in renal tubular amino acid reabsorption.

The degradation of glutathione in the kidney of the rat was investigated in vivo and in vitro. When radioactive glutathione or its analogue ophthalmic acid was administered intravenously to mice or rats, the tripeptides were rapidly and completely degraded. Within the organs, no radioactive glutathione, but only labelled glycine was found. The main part of the degrading activity was localized in the kidney. Kidney homogenate degraded glutathione at a rate of 46.5 nmoles/min per mg of protein. This could be inhibited by the gamma-glutamyltransferase inhibitor serine-borate. Isolated renal tubules degraded the tripeptide at a rate of 18 nmoles/min/mg; this reaction was also inhibited by serine-borate. The whole activity was found in the particulate fraction (100000 xg). Glycine and gamma-glutamylglycine were identified as the radio-active products. The results indicate that gamma-glutamyltransferase is able to split glutathione extracellularly in the lumen of the tubule at a very high rate. It is concluded that the enzyme faces the luminal side of the brush border membrane with respect to its substrate gluthathione. This seems to be incompatible with a basic topological prerequisite for the in vivo function of the gamma-glutamyl cycle in renal tubular amino acid reabsorption.