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

Abstract

ABSTRACT-y-Glutamyl transpeptidase catalyzes transfer of the y-glutamyl moiety of glutathione (and other y-glutamyl compounds) to amino acid and peptide acceptors; this reaction probably involves (a) formation of a y-glutamyl enzyme and (b) reaction of the y-glutamyl-enzyme with an acceptor. Maleate decreases the latter reaction and markedly increases hydrolysis of the y-glutamyl donor, apparently by affecting the enzyme so as to facilitate reaction of the y-glutamyl enzyme with water. Transpeptidase catalyzes y-glutamyl hydroxamate formation from many y-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 y-glutamyl-glutamine by the transpeptidase; in the presence of maleate, hydrolysis of glutamine is markedly (>10-fold) increased, as is also its conversion to -y-glutamyl hydroxamate in the presence of hydroxylamine. The findings suggest that the previously described "maleate-stimulated phosphate-independent glutaminase" is a catalytic function of -y-glutamyl transpeptidase. Transpeptidase-catalyzed glutaminase activity may play a role in renal ammoniagenesis. The ability of maleate to decrease transpeptidation of y-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 y-glutamyl cycle in amino-acid transport.

Ammoniagenesis: D-Glutamyltransferase as a Source of Ammonia in the Rat Kidney

“…This is not too surprising since the natural substrate far 7-GTP is actually glutathione, while gln is a very poor substrate for this enzyme (7). However, recent studies have shown that r-CTP can, in fact, hydrolyze gln (2) and at surprisingly high rate in the presence of maleate (8). Therefore, it is important to know what percentage of the total ;ammonia produced derives from u-GT under conditions approaching those found liz ~ltvo.…”

Induction and Inhibition of Tumor Progression

“…In further support, the progressing agent diethyl maleate has been shown to deplete cellular GSH. Although it has the ability to interact directly with GSH, diethyl maleate also stimulates the activity of GGT (41). Such an effect would also lead to an increase in cysteinylglycine with associated oxidative damage.…”

The Mechanism of the Formation of γ-Glutamylpeptides duringl-Glutamic Acid Fermentation Contributed Solely by γ-Glutamyltranspeptidase

“…L-Maleate known to inhibit the transpeptidation and facilitate the hydrolysis of r-glutamylpeptides catalyzed by mammalian enzyme 6 ) was found to be inactive to the bacterial enzyme.…”