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Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1; Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5; and Department of Clinical Chemistry, Huddinge University Hospital, Karolinska Institute, S-141 86 Huddinge, Sweden
This study
investigated whether dichloroacetate (DCA) decreases the reliance on
substrate level phosphorylation during the transition from rest to
moderate-intensity exercise in humans. Nine subjects cycled at ~65%
of maximal oxygen uptake
(
O2 max) after a
saline or DCA (100 mg/kg body wt) infusion, with muscle biopsies taken
at rest and at 30 s and 2 and 10 min of exercise. DCA infusion
increased pyruvate dehydrogenase (PDH) activation at rest (4.0 ± 0.3 vs. 0.9 ± 0.1 mmol · kg wet
wt
1 · min1)
and at 30 s (3.6 ± 0.2 vs. 2.5 ± 0.4 mmol · kg1 · min1)
of exercise. As a result, acetyl-CoA (45.9 ± 5.9 vs. 11.3 ± 1.5 µmol/kg dry wt) and acetylcarnitine (13.1 ± 1.0 vs. 1.6 ± 0.3 mmol/kg dry wt) were markedly increased by DCA infusion at rest. These
differences were maintained at 30 s and 2 min for both acetyl-CoA and
acetylcarnitine. Resting muscle lactate and phosphocreatine (PCr) were
not different between trials, but DCA infusion resulted in lower
lactate accumulation throughout exercise, especially at 2 min (21.6 ± 3.1 vs. 44.6 ± 8.0 mmol/kg dry wt). PCr utilization in the initial 30 s (16.9 ± 0.4 vs. 31.7 ± 2.6 mmol/kg dry wt) and 2 min (27.8 ± 4.7 vs. 45.1 ± 2.6 mmol/kg dry wt) of exercise was decreased with
DCA. This resulted in a lower accumulation of free inorganic phosphate
at 30 s (25.4 ± 2.0 vs. 36.4 ± 2.8 mmol/kg dry wt) and 2 min (34.6 ± 4.7 vs. 50.5 ± 2.2 mmol/kg dry wt) with DCA and
decreased glycogenolysis over 10 min. The data from this study support
the hypothesis that increased provision of substrate by DCA infusion
increases oxidative metabolism during the rest-to-work transition,
resulting in decreased PCr utilization and an improved cellular energy
state at the onset of exercise. The transitory improvement in energy
state decreased glycogenolysis and lactate accumulation during
moderate-intensity exercise.
glycogenolysis; lactate; phosphocreatine; inorganic phosphate; oxidative metabolism; pyruvate dehydrogenase activity; acetyl-coenzyme A; acetylcarnitine
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