A role for bicarbonate in the regulation of mammalian glutamine metabolism.
1. The concentration of HCO3- (independent of any change of pH) exerts different effects on glutamine metabolism in rat kidney-cortex tubules, hepatocytes and enterocytes.2. In kidney tubules HCO3- (10.5-50 MM) has no effect on glutaminase (EC 3.5.1.2), whereas glutamate dehydrogenase (EC 1.4.1.3) is inhibited as HCO3- concentration is increased. The result is that flux through the entire glutamate-to-glucose pathway is inhibited by increasing HCO3- concentrations. A large proportion (more than 30%) of the glutamine removed undergoes complete oxidation. 3. In hepatocytes, and to a smaller extent in enterocytes, HCO3- is an accelerator of glutaminase. Synthesis of glucose and urea from glutamine in hepatocytes increases as HCO3- concentration is increased. Calculations show that fumarate, formed via aspartate aminotransferase and arginino-succinate lyase, is the precursor of the glucose. There is no complete oxidation of the carbon skeleton of glutamine in hepatocytes. 4. Leucine at near-physiological concentrations (0.1-1 mM) is an accelerator of glutaminase in hepatocytes, but not in kidney tubules or in enterocytes. 5. The results are discussed in relation to regulation of acid/base balance in vivo.
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D001639:Bicarbonates; D005973:Glutamine; D005969:Glutamate Dehydrogenase; D005972:Glutaminase; D007930:Leucine