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 that 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.