Regulation of renal ammoniagenesis in the dog with chronic metabolic acidosis: effect of a glutamine load.
We recently emphasized that ATP is an obligatory product of renal glutamine metabolism and that all cells must remain in ATP balance. Based on this, we suggested that the maximum rate of renal ammoniagenesis in dogs with chronic metabolic acidosis may be limited by the rate of ATP utilization in the kidney. Since a large infusion of glutamine led to a twofold increase in renal ammoniagenesis in acidotic dogs, we wished to evaluate the renal metabolic changes that permitted this increment within the constraints of renal ATP balance. A large glutamine infusion did not lead to an augmented rate of ATP hydrolysis because renal oxygen consumption was not increased. Two major metabolic changes could explain this stimulation while maintaining ATP balance: first, ATP production from lactate by the kidney was decreased following the glutamine infusion; second, the metabolic fate of glutamine was changed so that more ammonium per ATP was synthesized (i.e., the rates of amino acid release into the renal vein were markedly enhanced, and gluconeogenesis was now a quantitatively significant process). 3-Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, when infused with glutamine, apparently decreased the calculated rate of gluconeogenesis as expected; however, ammonium production did not decline, because the rate of amino acid release increased further, as did the rate of oxygen consumption. Therefore, a large glutamine infusion increased renal ammoniagenesis in dogs with chronic metabolic acidosis while maintaining ATP balance, because ATP production from other substrates was decreased and because the fate of glutamine metabolism was altered in that less ATP was formed per glutamine utilized.
D000138:Acidosis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000096:biosynthesis*; D000818:Animals; D001158:Arteries; D002908:Chronic Disease; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005973:Glutamine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D010848:Picolinic Acids / Q000494:pharmacology
D010848:Picolinic Acids; D005973:Glutamine; D000641:Ammonia; C008363:3-mercaptopicolinic acid; D000255:Adenosine Triphosphate