Substrate and pH effects on glutamine synthesis in rat liver. Consequences for acid-base regulation
- 15 September 1991
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 278 (3), 709-714
- https://doi.org/10.1042/bj2780709
Abstract
Switching in acidosis of hepatic nitrogen disposal from urea synthesis to NH4+ and net glutamine production was demonstrated in the isolated perfused livers of starved male Wistar rats. Lactate was preferred to glucose as the substrate for the carbon skeleton of glutamine synthesized over the pH range 6.9-7.5. This is necessary if the switch away from a proton-producing process (ureagenesis) in acidosis is to constitute an acid-base regulating system intrinsic to the liver. Glutamine balance shifted with pH from marked net uptake to small net output under acidotic conditions (pH 7.5-6.9), an effect due solely to a decrease in glutamine uptake. NH4+ uptake by the liver had a linear relationship with pH, being markedly decreased in acidosis because glutamine synthesis was insufficient to compensate for the decreased incorporation into urea. Animals rendered chronically acidotic showed a lower central venous plasma urea concentration and a raised NH4+ concentration, but their livers synthesized no more glutamine when perfused at an acidotic pH than did normal livers. We conclude that perivenous hepatocytes may not be efficient scavengers of NH4+ ions, which must be partly disposed of elsewhere by non-proton-generating pathways if inhibition of ureagenesis is to represent a hepatic acid-base regulating system.Keywords
This publication has 18 references indexed in Scilit:
- Functional hepatocyte heterogeneityEuropean Journal of Biochemistry, 1989
- Interorgan glutamine flow in metabolic acidosisAmerican Journal of Physiology-Renal Physiology, 1987
- Metabolic aspects of the regulation of systemic pHAmerican Journal of Physiology-Renal Physiology, 1987
- Isolated Perfused Rat Liver: An Experimental Model for Studies on Ammonium and Amino Acid MetabolismTransfusion Medicine and Hemotherapy, 1987
- The effect of urea synthesis on extracellular pH in isolated perfused rat liverBiochemical Journal, 1986
- Functional hepatocyte heterogeneity in ammonia metabolism: The intercellular glutamine cycleJournal of Hepatology, 1985
- Hepatic urea synthesis and pH regulation. Role of CO2, HCO-3, pH and the activity of carbonic anhydraseEuropean Journal of Biochemistry, 1985
- Gluconeogenesis in periportal and perivenous hepatocytes of rat liver, isolated by a new high-yield digitonin/collagenase perfusion techniqueBiochemical Journal, 1985
- The mechanism of inhibition of ureogenesis by acidosisBioscience Reports, 1984
- Regulation of flux through glutaminase and glutamine synthetase in isolated perfused rat liverBiochimica et Biophysica Acta (BBA) - General Subjects, 1983