Ammonia partitioning between glutamine and urea: Interorgan participation in metabolic acidosis

Ammonia partitioning between glutamine and urea: Interorgan participation in metabolic acidosis. The distribution of precursor nitrogen between urea and glutamine was studied in control and acidotic rats. Acidosis, either acutely induced with hydrochloric acid or chronically induced with ammonium chloride, resulted in a rise in ammonia and a fall in urinary urea excretion; the percent of urinary nitrogen excreted as ammonia rose from 3.5 ± 0.4 and 4.9 ± 0.5 in fed and pair-fed controls to 25.9 ± 3.9 and 37 ± 5 in acidosis induced by hydrochloric acid and ammonium chloride. Hepatoportal vein urea concentration differences were significantly reduced, whereas glutamine concentration differences were significantly elevated, consistent with a shift of nitrogen from ureagenesis to glutamine; alanine and ammonia concentration differences were significantly decreased and increased respectively in the acidotic animals, suggesting the former supported urea synthesis whereas ammonia may preferentially support glutamine synthesis. Evidence of a feed-forward involvement of the gut in influencing hepatic nitrogen distribution was suggested by an increased ammonia and decreased alanine release in acidotic rats. Bilateral ureteral ligation was performed on control and acidotic rats to determine the fate of the redirected urinary ammonia. Ammonia did not accumulate in the blood, rather it was initially incorporated into glutamine, elevating the plasma level, and then it was subsequently deposited into urea. The shift of nitrogen back into urea in acidotic animals was confirmed by the greater postligation urea production rates supported by hepatic uptake of both alanine and glutamine. These results are discussed in terms of interorgan participation involving the liver, gut, and muscle in the partitioning of nitrogen between glutamine and urea. Repartition de l'ammoniaque entre la glutamine et l'uree: Participation de plusieurs organes a l'acidose metabolique. La distribution de l'azote precurseur entre l'uree et la glutamine a ete etudiee chez des rats controles et acidotiques. L'acidose, aussi bien celle determinee de facon aigue par acide chlorhydrique que celle induite de facon chronique par chlorure d'ammonia, a pour consequence une augmentation de l'ammoniurie et une diminution de l'excretion d'uree. Le pourcentage de l'azote urinaire excrete sous forme d'ammoniaque augmente de 3,5 ± 0,4 et 4,9 ± 0,5 chez les controles nourris a 25,9 ± 3,9 et 37 ± 5 dans l'acidose par acide chlorhydrique et chlorure d'ammonia. La difference veineuse hepatoportale de concentration d'uree etait considerablement reduite alors que celle de glutamine augmentait significativement ce qui etait compatible avec un deplacement de l'azote de l'ureogenese vers la glutamine. Les differences de concentration de l'alanine et de l'ammoniaque etaient respectivement diminuee et augmentee chez les animaux en acidose ce qui suggere que l'alanine servait la synthese d'uree alors que l'ammoniaque etait utilise preferentiellement a la synthese de glutamine. L'implication du tube digestif dans le controle de la distribution hepatique de l'azote etait suggeree par une augmentation de la liberation d'ammoniaque et une diminution de celle d'alanine chez des rats acidotiques. Des ligatures ureterales bilaterales ont ete realisees chez les rats controles et acidotiques afin de determiner le devenir de l'ammoniaque urinaire. L'ammoniaque ne s'est pas accumule dans le sang mais il s'est incorpore dans la glutamine, elevant la concentration plasmatique, puis il est apparu dans l'uree. Le retour de l'azote a l'uree chez les animaux acidotiques a ete confirme par les debits de production d'uree plus grands assures par la captation hepatique a la fois d'alanine et de glutamine. Ces resultats sont discutes en termes de participation de plusieurs organes impliquant le foie, l'intestin et le muscle dans la repartition de l'azote entre la glutamine et l'uree.