PDH activation by dichloroacetate reduces TCA cycle intermediates at rest but not during exercise in humans.

  • Gibala M
  • Saltin B
  • Physiol J
 et al. 
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Abstract

We hypothesized that dichloroacetate (DCA), which stimulates the pyruvate dehydrogenase complex (PDH), would attenuate the increase in muscle tricarboxylic acid cycle intermediates (TCAI) during exercise by increasing the oxidative disposal of pyruvate and attenuating the flux through anaplerotic pathways. Six subjects were infused with either saline (Con) or DCA (100 mg/kg body mass) and then performed a moderate leg kicking exercise for 15 min, followed immediately by intense exercise until exhaustion (Exh; approximately 4 min). Resting active fraction of PDH (PDH(a)) was markedly increased (P

Author-supplied keywords

  • Adult
  • Citric Acid Cycle
  • Citric Acid Cycle: drug effects
  • Dichloroacetic Acid
  • Dichloroacetic Acid: pharmacology
  • Enzyme Activation
  • Enzyme Activation: physiology
  • Exercise
  • Exercise: physiology
  • Female
  • Humans
  • Leg
  • Leg: physiology
  • Male
  • Pyruvate Dehydrogenase Complex
  • Pyruvate Dehydrogenase Complex: metabolism
  • Rest

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Authors

  • Martin J Gibala

  • Bengt Saltin

  • J Appl Physiol

  • Kristen D Dawson

  • Krista R Howarth

  • Mark A Tarnopolsky

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