Integrative physiology of splanchnic glutamine and ammonium metabolism

The substrates for hepatic ureagenesis are equimolar amounts of ammonium an d aspartate. The study design mimics conditions in which the liver receives more NH4+ than aspartate precursors (very low-protein diet). Fasted dogs, fitted acutely with transhepatic catheters, were infused with a tracer amou nt of (NH4Cl)-N-15. From arteriovenous differences, the major NH4+ precurso r for hepatic ureagenesis was via deamidation of glutamine in the portal dr ainage system (rather than in the liver), because there was a 1:1 stoichiom etry between glutamine disappearance and NH4+ appearance, and the amide (bu t not the amine) nitrogen of glutamine supplied the N-15 added to the porta l venous NH4+ pool. The liver extracted all this NH4+ from glutamine deamid ation plus an additional amount in a single pass, suggesting that there was an activator of hepatic ureagenesis. The other major source of nitrogen ex tracted by the liver was [N-14]alanine. Because alanine was not produced in the portal venous system, we speculate that it was derived ultimately from proteins in peripheral tissues.