RESPONSE OF HEPATIC AMINO-ACID CONSUMPTION TO CHRONIC METABOLIC-ACIDOSIS

In a previous paper, we showed that an inhibition of amino acid transp ort across the liver plasma membrane is responsible for the decrease i n urea synthesis in acute metabolic acidosis. We have now studied the mechanism responsible for the decline in urea synthesis in chronic aci dosis. Chronic metabolic acidosis and alkalosis were induced by feedin g three groups of rats HCl, NH4Cl, and NaHCO3 (8 mmol/day) for 7 days, Amino acids and NH4+ were measured in portal vein, hepatic vein, and aortic plasma, and arteriovenous differences were calculated. The rate s of urinary urea and NH4+ excretion were also determined. Hepatic ami no acid consumption was lower in both HCl and NH4Cl acidosis compared with NaHCO3-fed rats. Glutamine release was not different in the three conditions. Because intrahepatic concentrations of amino acids and in tracellular protein degradation were similar under these conditions, i t can be concluded that at low blood pH amino acid catabolism may be i nhibited and might explain the observed decrease in urea excretion in HCl, but not NH4Cl, acidosis; urea excretion was comparable in the NH4 Cl and NaHCO3 groups presumably because the increased NH4+ load in the former group was processed, uninhibited, to urea, Amino acids not use d by the liver in acidosis could account for the 25-fold increase in N H4+ excretion in HC1 and NH4Cl compared with alkalosis (P < 0.05). The se findings indicate that urea synthesis is decreased in chronic HCl a cidosis. They show that urea synthesis is controlled in chronic, as in acute, acidosis by amino acid uptake by the liver and/or intrahepatic degradation and that the ornithine cycle per se has only minor contro l of acid-base homeostasis.