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

Abstract
The metabolism in vivo of .gamma.-glutamyl amino acids and peptides was studied in the mouse after administration of loading doses of L-.gamma.-glutamyl-2-aminobutyrate and several other .gamma.-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-.gamma.-[14C]glutamyl-L-2-aminobutyrate a rapid incorporation of label into kidney glutamate, glutamine and aspartate was found. Both the hydrolytic and .gamma.-glutamyl transfer reactions catalyzed by .gamma.-glutamyl transpeptidase [EC 2.3.2.2] may be active in the renal handling of .gamma.-glutamyl compounds. Indirect evidence was obtained that L-.gamma.-glutamyl-2-aminobutyrate is partially taken up by the kidney cell in an intact form. In contrast to the kidney, administration of several .gamma.-glutamyl derivatives did not cause an increase in liver glutamate, glutamine and pyrrolidone carboxylate. After administration of L-.gamma.-glutamyl-2-aminobutyrate only a slight increase in liver aspartate and pyrrolidone carboxylate was observed. Experiments with L-.gamma.-[14C]glutamyl-L-2-aminobutyrate suggest that this derivative is largely 1st degraded to its component amino acids (probably in the kidney) before entering into the metabolism of the liver cell. .gamma.-Glutamyl transpeptidase may function in the metabolism and transport of glutathione and other .gamma.-glutamyl compounds in a manner analogous to the function of dipeptidases and disaccharidases in the metabolism and transport of dipeptides and disaccharides, respectively.
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