title: Renal glutaminases: Diamox inhibition of glutamyltransferase.
abstract: Ammonia (NH3) production by the rat kidney was studied after an acute administration of acetazolamide (Diamox). Diamox reduced renal ammonia release (renal vein NH3 + urine NH3 - arterial NH3) 60 PERCENT IN The intact functioning kidney. Ammonia production by whole-kidney homogenates was decreased by Diamox, confirming the drug's action as inhibiting glutaminase activity. Additional studies demonstrated the inhibited glutaminase was localized in the cytoplasm; the glutaminase activity of the mitochondrial fraction was unaffected by Diamox. Isolated perfused kidneys from Diamox-treated rats confirmed that the drug reduced ammonia production by inhibiting glutamyltransferase; in addition, inhibition was shown to be of a competitive nature. We therefore conclude that cytoplasmic glutamyltransferase is the major producer of ammonia in the nonacidotic rat kidney and that it is competitively inhibited by Diamox.
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000641:Ammonia / Q000096:biosynthesis / Q000652:urine; D000818:Animals; D001667:Binding, Competitive; D003593:Cytoplasm / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism*; D005973:Glutamine / Q000097:blood; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology* / Q000648:ultrastructure; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D051381:Rats
chemical_list: D005973:Glutamine; D000641:Ammonia; D000123:Acetyltransferases; D005972:Glutaminase; D000086:Acetazolamide