Regulation of interorganal glutamine flow in metabolic acidosis.
Metabolic acidosis redirects interorgan glutamine flow from hepatic utilization to renal ammoniagenesis at the expense of ureagenesis. The roles of arterial glutamine load and organ glutaminase capacity in the regulation of glutamine balance across the gut, liver, and kidneys were studied in control and chronically acidotic rats. In control rats these organs combined to remove 733 nmol glutamine X min-1 X 100 g-1 in agreement with their respective glutaminase content, gut greater than liver greater than kidneys. In chronic metabolic acidosis renal glutamine extraction alone increased to 1,158 nmol X min-1 X 100 g-1 associated with an increased glutaminase capacity. However, the total glutamine deficit across these organs rose to only 1,043 nmol glutamine consumed X min-1 X 100 g-1 as a consequence of hepatic glutamine uptake reversing to net release. This reversal was not dependent on increased hepatic glutamine synthetase capacity, but rather appears to be dependent on the combined effect of reduced portal venous glutamine load and increased ammonia load. The reduction in portal glutamine load is, in turn, a consequence of renal glutamine extraction and reduced arterial glutamine concentration in metabolic acidosis as well as maintained gut glutamine extraction. Elevating arterial glutamine concentration in metabolic acidosis has no effect on renal uptake, but enhances splanchnic bed extraction with the restoration of ureagenesis. Thus the interorgan flow of glutamine and deposition of N into either urea or ammonia appears to be dependent on arterial glutamine concentration and hence glutamine availability in chronic metabolic acidosis in the rat.
D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000378:metabolism*; D000641:Ammonia / Q000096:biosynthesis; D000818:Animals; D001693:Biological Transport, Active; D001806:Blood Urea Nitrogen; D005973:Glutamine / Q000378:metabolism*; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008433:Mathematics; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000096:biosynthesis
D005973:Glutamine; D000641:Ammonia; D014508:Urea