Considerable debate surrounds the issue of whether the rate of adaptation of skeletal muscle O₂ consumption (O₂) at the onset of exercise is limited by 1) the inertia of intrinsic cellular metabolic signals and enzyme activation or 2) the availability of O₂ to the mitochondria, as determined by an extrinsic inertia of convective and diffusive O₂ 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 (P_mitoO₂). Changes in both phosphorylation and redox potential are determined by intrinsic metabolic inertia. P_mitoO₂ is determined by the extrinsic inertia of both convective and diffusive O₂ transport mechanisms during the adaptation to exercise and the rate of mitochondrial O₂ utilization. In a number of exercise conditions, P_mitoO₂ 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, O₂ consumption. The availability of reducing equivalents and O₂ would modulate the rate of adaptation of O₂.

muscle energetics; mitochondrial respiration; oxygen delivery; exercise

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