Metabolism of γ‐Glutamyl Amino Acids and Peptides in Mouse Liver and Kidney in vivo

Abstract

The metabolism in vivo of γ‐glutamyl amino acids and peptides was studied in the mouse after administration of loading doses of l‐γ‐glutamyl‐2‐aminobutyrate and several other γ‐glutamyl compounds, including glutathione. A great and rapid accumulation of glutamate, glutamine, aspartate and pyrrolidone carboxylate was observed in the kidney. Similarly, after administration of a tracer dose of l‐γ‐[14C]glutamyl‐l‐2‐aminobutyrate a rapid incorporation of label into kidney glutamate, glutamine and aspartate was found. These results suggest that both the hydrolytic and γ‐glutamyl transfer reactions catalyzed by γ‐glutamyl transpeptidase are active in the renal handling of γ‐glutamyl compounds. Indirect evidence was obtained that l‐γ‐glutamyl‐2‐aminobutyrate is partially taken up by the kidney cell in an intact form. In contrast to the kidney, administration of several γ‐glutamyl derivatives did not cause an increase in liver glutamate, glutamine and pyrrolidone carboxylate. After administration of l‐γ‐glutamyl‐2‐aminobutyrate only a slight increase in liver aspartate and pyrrolidone carboxylate was observed. Experiments with l‐γ‐[14C]glutamyl‐l‐2‐aminobutyrate suggest that this derivative is largely first degraded to its component amino acids (probably in the kidney) before entering into the metabolism of the liver cell. γ‐Glutamyl transpeptidase may function in the metabolism and transport of glutathione and other γ‐glutamyl compounds in a manner analogous to the function of dipeptidases and disaccharidases in the metabolism and transport of dipeptides and disaccharides respectively. Copyright © 1976, Wiley Blackwell. All rights reserved