Stimulation of the hydrolytic activity and decrease of the transpeptidase activity of gamma-glutamyl transpeptidase by maleate; identity of a rat kidney maleate-stimulated glutaminase and gamma-glutamyl transpeptidase.
gamma-Glutamyl transpeptidase catalyzes transfer of the gamma-glutamyl moiety of glutathione (and other gamma-glutamyl compounds) to amino acid and peptide acceptors; this reaction probably involves (a) formation of a gamma-glutamyl enzyme and (b) reaction of the gamma-glutamyl-enzyme with an acceptor. Maleate decreases the latter reaction and markedly increases hydrolysis of the gamma-glutamyl donor, apparently by affecting the enzyme so as to facilitate reaction of the gammaglutamyl enzyme with water. Transpeptidase catalyzes gamma-glutamyl hydroxamate formation from many gamma-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 gamma-glutamyl-glutamine by the transpeptidase; in the presence of maleate, hydrolysis of glutamine is markedly (>10-fold) increased, as is also its conversion to gamma-glutamyl hydroxamate in the presence of hydroxylamine. The findings suggest that the previously described "maleate-stimulated phosphate-independent glutaminase" is a catalytic function of gamma-glutamyl transpeptidase. Transpeptidase-catalyzed glutaminase activity may play a role in renal ammoniagenesis. The ability of maleate to decrease transpeptidation of gamma-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 gamma-glutamyl cycle in amino-acid transport.
D000641:Ammonia / Q000096:biosynthesis; D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D003864:Depression, Chemical; D005972:Glutaminase / Q000378:metabolism*; D005973:Glutamine; D005978:Glutathione; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D006898:Hydroxylamines; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D008298:Maleates / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D002250:Carbon Radioisotopes; D006898:Hydroxylamines; D008298:Maleates; D005973:Glutamine; D000641:Ammonia; D005723:gamma-Glutamyltransferase; D005972:Glutaminase; D005978:Glutathione