Effect of dichloroacetate on lactate concentration in exercising humans.
The precise mechanism responsible for the increase in plasma lactate concentration during exercise in humans is not known. We have used dichloroacetate to test the hypothesis that a limitation in pyruvate dehydrogenase activity is responsible for the rise in plasma lactate. Dichloroacetate stimulates the activity of pyruvate dehydrogenase, which is normally the regulatory enzyme in the oxidation of glucose when tissue oxygenation is adequate. Six subjects were studied twice according to a randomized, crossover protocol, involving one test with saline infusion and another with dichloroacetate infusion. Exercise load on a bicycle ergometer was increased progressively until exhaustion. Blood samples were drawn each minute throughout exercise and periodically throughout 120 min of recovery. Dichloroacetate significantly lowered the lactate concentration during exercise performed at less than 80% of the average maximal O2 consumption. The peak concentration of lactate at exhaustion was not affected by dichloroacetate treatment, but dichloroacetate did lower lactate concentration throughout recovery. These results suggest that a limitation in pyruvate dehydrogenase activity contributes to the increase in plasma lactate during submaximal exercise and recovery.
Carraro
F
F
Metabolism Unit, Shriners Burns Institute, Galveston, Texas.
Klein
S
S
Rosenblatt
J I
JI
Wolfe
R R
RR
D000085:Acetates / Q000494:pharmacology*; D000328:Adult; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D006801:Humans; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D008297:Male; D008954:Models, Biological; D008962:Models, Theoretical; D010101:Oxygen Consumption; D005082:Physical Exertion; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D000085:Acetates; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D003999:Dichloroacetic Acid