Response of hepatic amino acid consumption to chronic metabolic
acidosis.
Boon, L., P. J. E. Blommaart, A. J. Meijer, W. H. Lamers, and A. C.
Schoolwerth.
Department of Anatomy and Embryology, University of Amsterdam, The
Netherlands; E.C. Slater Institute for Biochemical Research,
University of Amsterdam; Department of Internal Medicine, Medical
College of Virginia, Virginia, Commonwealth University, Richmond,
Virginia
APStracts 3:0057F, 1996.
In a previous paper, we showed that an inhibition of amino acid
transport across the liver plasma membrane is responsible for the
decrease in urea synthesis in acute metabolic acidosis. We have now
studied the mechanism responsible for the decline in urea synthesis
in chronic acidosis. Chronic metabolic acidosis and alkalosis were
induced by feeding 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 rates of urinary urea and NH4+ excretion were
also determined. Hepatic amino acid consumption was lower in both HCl
and NH4Cl acidosis compared to NaHCO3-fed rats. Glutamine release was
not different in the three conditions. Since intrahepatic
concentrations of amino acids and intracellular protein degradation
were similar under these conditions, it can be concluded that at low
blood pH amino acid catabolism may be inhibited and might explain the
observed decrease in urea excretion in HCl, but not NH4Cl, acidosis;
urea excretion was comparable in the NH4Cl and NaHCO3 groups
presumably because the increased NH4+ load in the former group was
processed, uninhibited, to urea. Amino acids not used by the liver in
acidosis could account for the 25-fold increase in NH4+ excretion in
HCl and NH4Cl compared to alkalosis (p<0.05). These findings
indicate that urea synthesis is decreased in chronic HCl acidosis.
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
control of acid-base homeostasis.
Received 7 August 1995; accepted in final form 29 February 1996.
APS Manuscript Number F260-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96