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Abstract #0745

Activation of Skeletal Muscle PDH with DCA Increases Steady State ΔGATP Below The Aerobic Threshold

Jonathan David Kasper 1 , Anne Tonson 1 , Mike Klingler 1 , Joshua Hubert 1 , Ronald Meyer 2 , and Robert Wiseman 2

1 Physiology, Michigan State University, East Lansing, Michigan, United States, 2 Physiology and Radiology, Michigan State University, East Lansing, Michigan, United States

Skeletal muscle is a thermodynamic system and its energetic state is determined by the magnitude of the mitochondrial redox, proton motive force, and ΔGATP potentials. Pyruvate dehydrogenase (PDH) flux is directly linked to NADH production and influences mitochondrial redox potential. This study sought to evaluate the effect of PDH activation on muscle energetics. Pharmacological activation of PDH results in elevation of steady state ΔGATP at rest and during stimulation below the aerobic threshold of muscle contraction. This effect is attributed to elevation of steady state redox potential and implicates PDH as an important site of regulation for skeletal muscle energetics.

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