Mitochondrial coupling in humans: assessment of the P/O₂ ratio at the onset of calf exercise

Coupling of oxidation to ATP synthesis (P/O₂ ratio) is a critical step in the conversion of carbon substrates to fuel (ATP) for cellular activity. The ability to quantitatively assess mitochondrial coupling in vivo can be a valuable tool for basic research and clinical purposes. At the onset of a square wave moderate exercise, the ratio between absolute amount of phosphocreatine split and O₂ deficit (corrected for the amount of O₂ released from the body O₂ stores and in the absence of lactate production), is the mirror image of the P/O₂ ratio. To calculate this value, cardiac output \({(\dot{Q}),}\) whole body O₂ uptake \({(\dot{V}{\rm O}_{2}),}\) O₂ deficit \({\left( {{\text{O}}^{{{\text{def}}}}_{{\text{2}}} } \right)}\) and high-energy phosphates concentration (by ³¹P-NMR spectroscopy) in the calf muscles were measured on nine healthy volunteers at rest and during moderate intensity plantar flexion exercise (3.44 ± 0.73 W per unit active muscle mass). \({\dot{Q}}\) and \({\dot{V}{\rm O}_{2}}\) increased (from 4.68 ± 1.56 to 5.83 ± 1.59 l min⁻¹ and from 0.28 ± 0.05 to 0.48 ± 0.09 l min⁻¹, respectively), while phosphocreatine (PCr) concentration decreased significantly (22 ± 6%) from rest to steady-state exercise. For each volunteer, “gross” \({{{\text{O}}^{{{\text{def}}}}_{{\text{2}}}}}\) was corrected for the individual changes in the venous blood O₂ stores \(({{\text{representing 49}}{\text{.9 $ \pm $ 9}} {\text{.5\% of the gross O}}^{{{\text{def}}}}_{2} })\) yielding the “net” \({{{\text{O}}^{{{\text{def}}}}_{{\text{2}}}}}\). Resting PCr concentration was estimated from the appropriate spectroscopy data. The so calculated P/O₂ ratio amounted on average to 4.24 ± 0.13 and was, in all nine subjects, very close to the literature values obtained directly on intact skeletal muscle. This unfolds the prospect of a non-invasive tool to quantitatively study mitochondrial coupling in vivo.