Abstract
In vivo, the final products of RBC glycolysis, pyruvate (PA) and lactate (LA), diffuse into the plasma, and a steady level of glycolytic intermediates is maintained within the cell. In vitro, when RBCs are incubated with glucose (GL) in a closed system, an increase in fructose-1, 6-diphosphate (FDP) and triose phosphates (TP) rapidly takes place, rising twenty-fold in 3 hours. This makes in vitro studies of glycolytic intermediates impossible. We have incubated RBCs in an open system that allows physiologic diffusion of the PA and LA produced. In this system, in the presence of GL alone, the accumulation of FDP and TP is markedly reduced, with a six-fold increase over normal. On addition of PA only, the accumulation of FDP and TP is suppressed, and steady state concentrations are observed. On addition of LA only, however, the accumulation of FDP and TP is again twenty-fold as in the closed system. On addition of both PA and LA, at the physiological ratio of 1/19, regardless of concentration, the accumulation of FDP and TP is suppressed, with levels similar to those observed with PA only. If LA is increased and the PA/LA ratio is significantly reduced, then accumulation of FDP and TP occurs. When LA increases in the RBCs, an accumulation of NADH takes place at the LDH step, and thus glycolysis is slowed at the level of the 3-phosphoglyceraldehyde dehydrogenase (3-PGAD) step, through NADH inhibition. An excess of pyruvate lowers the NADH concentration at the LDH step, in turn releasing the inhibition of 3-PGAD. These data suggest that the orderly flow of glycolysis in RBCs depends on the diffusion of the PA and LA produced, to maintain a constant intracellular PA/LA ratio, necessary to regulate the intracellular NAD/NADH ratio. An open system of incubation approximates closely physiologic conditions and its use allows control of glycolysis in vitro, with this technique it is possible to study in vitro glycolytic intermediate levels, in normal and abnormal conditions.
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Seaman, C., Jam Tilton, W., Smith, M. et al. 937 INTERACTION OF PYRUVATE/LACTATE AND NAD/NADH RATIOS IN THE REGULATION OF RED CELL (RBC) GLYCOLYSIS. Pediatr Res 19, 267 (1985). https://doi.org/10.1203/00006450-198504000-00967
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DOI: https://doi.org/10.1203/00006450-198504000-00967