ACUTE ACIDOSIS INHIBITS LIVER AMINO-ACID-TRANSPORT - NO PRIMARY ROLE FOR THE UREA CYCLE IN ACID-BASE-BALANCE

To examine further the role of the liver in acid-base homeostasis, we studied hepatic amino acid uptake and urea synthesis in rats in vivo d uring acute acidosis and alkalosis, induced by infusion of 1.8 mmol of HCl or NaHCO3 over 3 h. Amino acids and NH4+ were measured in portal vein, hepatic vein, and aortic plasma, and arteriovenous differences o f amino acids and urinary urea and NH4+ excretion were measured. In ac idosis, urinary urea excretion was reduced 36% (P < 0.01), whereas uri nary NH4+ excretion increased ninefold (P < 0.01), but the sum of urea and NH4+ excretion was unchanged. Total hepatic amino acid uptake, as determined from arteriovenous differences, was decreased by 63% (P < 0.01) in acidosis, with the major effect being noted with alanine and glycine. Only glutamine was released in both acidosis and alkalosis bu t was not significantly different in the two conditions. Since intrace llular concentrations of readily transportable amino acids were not di fferent at low pH despite accelerated protein degradation, these resul ts indicate that hepatic amino acid transport was inhibited markedly a nd sufficiently to explain the observed decrease in urea synthesis. To tal hepatic vein amino acid content was greater in acidosis than alkal osis (P < 0.01). Directly or indirectly, by conversion to glutamine el sewhere, these increased amino acids were degraded in kidney and accou nted for the ninefold increase in urinary NH4+ excretion. These findin gs indicate that in acute acidosis flux through the ornithine cycle is controlled by hepatic amino acid transport rather than by the activit y of the ornithine cycle per se; the findings argue against a primary role for the ornithine cycle in the regulation of acid-base homeostasi s.