EFFECT OF HCO3- ON GLUTAMINE AND GLUCOSE-METABOLISM IN LYMPHOCYTES

Lymphocytes play a quantitatively important role in glutamine utilizat ion in the body. We hypothesized that in metabolic acidosis characteri zed by decreased extracellular HCO3- concentration ([HCO3-]), glutamin e utilization by lymphocytes may decrease to compensate partially for the increased uptake of glutamine by the kidneys for ammoniagenesis. T his study was therefore designed to quantify the effect of extracellul ar [HCO3-] on glutamine metabolism in lymphocytes relative to glucose utilization. Mesenteric lymph node lymphocytes were incubated at 37 de grees C for 1 hour in Krebs-Henseleit buffer containing 0, 12.5, and 2 5 mmol/L HCO3- at a constant pH of 7.4 or 15.7 and 25 mmol/L HCO3- at a constant CO2 concentration of 1.25 mmol/L. Reducing extracellular [H CO3-] from 25 to 12.5 mmol/L at constant pH or from 25 to 15.7 mmol/L at constant CO2 concentration decreased glutamine utilization and the production of glutamate and ammonia. A reduction in [HCO3-] from 12.5 to 0 mmol/L further decreased glutamine utilization, as well as the pr oduction of all measured glutamine metabolites. Interestingly. decreas ing [HCO3-] from 25 to 0 mmol/L had no significant effect an glucose m etabolism. although the production of pyruvate (a minor product of glu cose in lymphocytes) was decreased in the absence of medium HCO3-. The contribution of glutamine but not of glucose to lymphocyte adenosine triphosphate (ATP) production was decreased with reduced extracellular [HCO3-]. Thus, glucose was a more important fuel for lymphocytes than was glutamine at low [HCO3-]. Our results demonstrate for the first t ime that a decrease in extracellular [HCO3-] reduces glutamine utiliza tion and metabolism by lymphocytes, which may help to increase the ava ilability of glutamine for renal ammoniagenesis under conditions of me tabolic acidosis. Copyright (C) 1995 by W.B. Saunders Company