Effects of inhibition and modulation of gamma-glutamyltransferase on glutamine and glutamate metabolism in control and acidotic rat proximal tubules.
The possible role of gamma-glutamyltransferase (gamma-GT) in renal ammonia production from glutamine remains controversial, prompting the current investigation. In rat proximal tubules, compounds known to activate the enzyme including the endogenously produced organic anion, hippurate, induced a significant increase in glutamine-ammoniagenesis both in nonacidosis and chronic metabolic acidosis although in absolute terms the increase was not more marked under the latter conditions. AT-125, which irreversibly inactivates gamma-GT, but not phosphate-dependent glutaminase, reduced the production of ammonia from glutamine in both acid-base states. In absolute terms, again, this reduction was similar under both acid-base conditions, implying an unimportant role for gamma-GT in vitro in the augmentation in renal ammoniagenesis induced by chronic metabolic acidosis. Maleate-stimulated glutamine-ammoniagenesis recently attributed to its intramitochondrial inhibitory effect in the dog is substantially due to the activation of gamma-GT in rat proximal tubules.
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism*; D006626:Hippurates / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005971:Glutamates; D006626:Hippurates; D007555:Isoxazoles; D005973:Glutamine; D018698:Glutamic Acid; D005723:gamma-Glutamyltransferase; C006303:acivicin; C030514:hippuric acid