Effect of HCO3- on glutamine and glucose metabolism in lymphocytes

Lymphocytes play a quantitatively important role in glutamine utilization in the body. We hypothesized that in metabolic acidosis characterized by decreased extracellular HCO3- concentration ([HCO3-]), glutamine utilization by lymphocytes may decrease to compensate partially for the increased uptake of glutamine by the kidneys for ammoniagenesis. This study was therefore designed to quantify the effect of extracellular [HCO3-] on glutamine metabolism in lymphocytes relative to glucose utilization. Mesenteric lymph node lymphocytes were incubated at 37 degrees C for 1 hour in Krebs-Henseleit buffer containing 0, 12.5, and 25 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 [HCO3-] 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 production of all measured glutamine metabolites. Interestingly, decreasing [HCO3-] from 25 to 0 mmol/L had no significant effect on glucose metabolism, although the production of pyruvate (a minor product of glucose 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-].(ABSTRACT TRUNCATED AT 250 WORDS)