Pyruvate Dehydrogenase Complex Activation Status and Acetyl Group Availability as a Site of Interchange between Anaerobic and Oxidative Metabolism during Intense Exercise

Abstract

During high intensity muscular contraction ATP is supplied at near maximal rates by PCr degradation and glycolysis. However, as exercise duration increases, the contribution of anaerobic ATP turnover to energy delivery declines due to the depletion of PCr stores and a reduction in the rate of glycogenolysis, which together may be responsible for the parallel reduction in muscle force production and power output. The importance of oxidative phosphorylation to total ATP production during intense muscle contraction has been underestimated to date. Recent studies have, however, demonstrated that the reduction in work production during repeated bouts of maximal exercise is less than the reduction observed in anaerobic energy provision. This observation has been suggested to reflect an increased contribution from oxidative phosphorylation to total energy production; but the mechanism responsible for this increased contribution is poorly understood. Recent evidence has pointed to the activation status of the pyruvate dehydrogenase complex and/or acetyl group availability as being focal in dictating temporal changes in ADP flux at the onset of intense exercise and, hence, the relative contribution made by anaerobic and oxidative ATP regenerating pathways under these conditions. As might be expected, therefore, maximising the contribution from oxidative ATP regeneration at the onset of exercise (by pharmacologically activating the pyruvate dehydrogenase complex prior to exercise) has been shown to have substantial functional benefits during high intensity contraction.

This body of work has also illustrated that, contrary to popular theory, a large proportion of muscle lactate accumulation at the onset of exercise is associated with a lag in the activation of oxidative ATP production rather than with a lag in oxygen delivery.