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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Sep;71(9):3329–3333. doi: 10.1073/pnas.71.9.3329

Stimulation of the Hydrolytic Activity and Decrease of the Transpeptidase Activity of γ-Glutamyl Transpeptidase by Maleate; Identity of a Rat Kidney Maleate-Stimulated Glutaminase and γ-Glutamyl Transpeptidase

Suresh S Tate 1, Alton Meister 1
PMCID: PMC433764  PMID: 4154442

Abstract

γ-Glutamyl transpeptidase catalyzes transfer of the γ-glutamyl moiety of glutathione (and other γ-glutamyl compounds) to amino acid and peptide acceptors; this reaction probably involves (a) formation of a γ-glutamyl enzyme and (b) reaction of the γ-glutamyl-enzyme with an acceptor. Maleate decreases the latter reaction and markedly increases hydrolysis of the γ-glutamyl donor, apparently by affecting the enzyme so as to facilitate reaction of the γglutamyl enzyme with water. Transpeptidase catalyzes γ-glutamyl hydroxamate formation from many γ-glutamyl compounds and hydroxylamine; this reaction is stimulated 4- to 5-fold by maleate. Glutamine, a poor substrate for transpeptidation as compared to glutathione, is slowly hydrolyzed and converted to γ-glutamyl-glutamine by the transpeptidase; in the presence of maleate, hydrolysis of glutamine is markedly (>10-fold) increased, as is also its conversion to γ-glutamyl hydroxamate in the presence of hydroxylamine. The findings suggest that the previously described “maleate-stimulated phosphate-independent glutaminase” is a catalytic function of γ-glutamyl transpeptidase. Transpeptidase-catalyzed glutaminase activity may play a role in renal ammoniagenesis. The ability of maleate to decrease transpeptidation of γ-glutamyl compounds (and to increase their hydrolysis to glutamate), when considered in the light of earlier findings that treatment of animals with maleate produces aminoaciduria, is consistent with function of transpeptidase and the γ-glutamyl cycle in amino-acid transport.

Keywords: amino-acid transport, ammoniagenesis, γ-glutamyl cycle, glutathione, glutamine

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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