During aerobic exercise (>65 of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate potential of rat gastrocnemius muscle during contraction. Twitch contractions were induced in vivo over a broad range of intensities to sample submaximal and maximal aerobic workloads. Muscle phosphorus metabolites were measured in vivo before and after DCA treatment by phosphorus nuclear magnetic resonance spectroscopy. At rest, DCA increased PDH activation compared with control (90 ± 12 vs. 23 ± 3, P < 0.05), with parallel decreases in inorganic phosphate (Pi) of 17 (1.4 ± 0.2 vs. 1.7 ± 0.1 mM, P < 0.05) and an increase in the free energy of ATP hydrolysis (AGatp) (-66.2 ± 0.3 vs. -65.6 ± 0.2 kJ/mol, P < 0.05).
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