Lactate and regulation of lung glycolytic rate

The effect of exogenous lactate on glycolytic rate was studied with the isolated perfused rat lung. Glucose utilization was estimated from the rate of 3H2O production from [5-3H]glucose, and lactate and pyruvate production was measured by perfusate assay. Glucose utilization was unaffected by addition of 0.5 mM lactate to the perfusate but decreased by 27% with 1 mM lactate. With 2 mM lactate, glucose utilization was decreased by 46% and lactate production decreased 95%. With addition of 0.2 mM pyruvate plus 2 mM lactate, glucose utilization was decreased 63% compared with control. These data indicate that the effect of lactate on glucose utilization was not through change in the cellular redox state. During lung anoxia produced by ventilation with CO, glucose utilization and lactate production were again markedly decreased by addition of lactate (2 mM) to the perfusate. However, addition of pyruvate plus lactate resulted in a markedly stimulated rate of glucose utilization. This result indicates that during anoxia the effect of lactate on glycolysis resulted from alteration of the redox ratio. This study indicates that lactate influences the rate of glycolysis in the normal lung through its utilization as a substrate for mitochondrial metabolism. During anoxia, changes in the lung redox state with lactate are a major determinant of the glycolytic rate.