The role of pyruvate in the oxidation of glucose and lactate

Abstract

The observation has been confirmed that the addition of pyruvate to ascites cells can stimulate the appearance of radioactive CO2 from labeled glucose or lactate. The effect was especially manifest at low concentrations of pyruvate. It is explained by assuming that the rate of pyruvate oxidation is limited by the rate of oxidation of reduced diphosphopyridine nucleotide and that exogenous pyruvate acts as an additional electron acceptor. The following observations support this interpretation: (a) the stimulation was primarily in the oxidation of glucose carbons 3 and 4; (b) an increased formation of lactate accompanied the stimulation by pyruvate; (c) stoichiometry in accord with a dismutation of pyruvate, two molecules of pyruvate disappearing per molecule of lactate produced, was observed under anaerobic conditions; (d) under conditions in which the oxidation of reduced diphosphopyridine nucleotide was not limiting, for example in the presence of an artificial electron acceptor such as phenazine methosulfate, or an uncoupling agent such as Dicumarol, pyruvate decreases the C14 incorporation of glucose or lactate into the respiratory CO2 in accord with the conventional metabolic pathways; (e) the relative rates of oxidation of pyruvate metabolically derived from glucose-C14 were comparable to the rates of oxidation of the individual carbons of added pyruvate-C14. It is concluded that it is not necessary to postulate either a new pathway for lactate oxidation nor a compartmentation of exogenous and endogenous pyrruvate to explain the pyruvate stimulatory effect, and that this effect is in accord with conventionally accepted reaction mechanisms.