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

Coupling of oxidation to ATP synthesis (P/O-2 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 O-2 deficit (corrected for the amount of O-2 released from the body O-2 stores and in the absence of lactate production), is the mirror image of the P/O-2 ratio. To calculate this value, cardiac output (<(Q)over dot >), whole body O-2 uptake (<(V)over dot > O-2), O-2 deficit (O-2(def)) and high-energy phosphates concentration (by P-31-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). <(Q)over dot > and <(V)over dot > 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" O-2(def) was corrected for the individual changes in the venous blood O-2 stores (representing 49 +/- 9.5% of the gross O-2(def). Resting PCr concentration was estimated from the appropriate spectroscopy data. The so calculated P/O-2 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.