Control of substrate utilization and metabolism in skeletal muscle of exercising humans

The overall purpose of this thesis was to examine the role of changes in mitochondrial potential on the time-dependent changes in muscle energy and substrate metabolism, and whole-body substrate turnover and oxidation, during prolonged endurance exercise training. Adaptations were examined early after the initiation of training (5 days) and following more prolonged periods of training (10 and 32 days), to elucidate the temporal nature of metabolic responses induced during the training program. All subjects were healthy, active but untrained, males. A 10 day training program resulted in tighter metabolic coupling between ATP demand and supply, evidenced by less depletion of phosphocreatine (PCr) and accumulation of inosine monophosphate (IMP). Training also resulted in a smaller accumulation of muscle lactate and less depletion of muscle glycogen, suggesting a reduction in glucose turnover and oxidation. Despite a reduced intramuscular accumulation of lactate, lactate Ra was unchanged following training.;In an additional study designed to examine the time-dependency of adaptations in muscle metabolism, oxygen uptake (VO;It is concluded that training induced rapid adaptations in cellular metabolism, indicative of a tighter metabolic coupling between ATP supply and demand, prior to increases in muscle oxidative potential. Potentiation of these adaptations occurs following longer periods of training. These changes may be mediated by the increase in muscle oxidative capacity, and also by adaptations in VO...