Interaction of factors determining oxygen uptake at the onset of exercise

Considerable debate surrounds the issue of whether the rate of adaptation of skeletal muscle O-2 consumption ((Q) over dot O-2) at the onset of exercise is limited by 1) the inertia of intrinsic cellular metabolic signals and enzyme activation or 2) the availability of O-2 to the mitochondria, as determined by an extrinsic inertia of convective and diffusive O-2 transport mechanisms. This review critically examines evidence for both hypotheses and clarifies important limitations in the experimental and theoretical approaches to this issue. A review of biochemical evidence suggests that a given respiratory rate is a function of the net drive of phosphorylation potential and redox potential and cellular mitochondrial PO2 (PmitoO2) Changes in both phosphorylation and redox potential are determined by intrinsic metabolic inertia. PmitoO2 is determined by the extrinsic inertia of both convective and diffusive O-2 transport mechanisms during the adaptation to exercise and the rate of mitochondrial O-2 utilization. In a number of exercise conditions, PmitoO2 appears to be within a range capable of modulating muscle metabolism. Within this context, adjustments in the phosphate energy state of the cell would serve as a cytosolic "transducer," linking ATP consumption with mitochondrial ATP production and, therefore, O-2 consumption. The availability of reducing equivalents and O-2 would modulate the rate of adaptation of (Q) over dot O-2.