Francescato MP, Cettolo V, di Prampero PE. Influence of phosphagen concentration on phosphocreatine breakdown kinetics. Data from human gastrocnemius muscle. J Appl Physiol 105: 158 -164, 2008. First published April 24, 2008 doi:10.1152/japplphysiol.00007.2008.-At the onset of a square-wave exercise of moderate intensity, in the absence of any detectable lactate production, the hydrolysis of phosphocreatine (PCr) fills the gap between energy requirement and energy yield by oxidative pathways, thus representing a readily available source of energy for the muscle. We verified experimentally the relationships between high-energy phosphates and/or their changes and the time constant of PCr concentration ([PCr]) kinetics in humans (PCr). High-energy phosphate concentration (by 31 P-NMR spectroscopy) in the calf muscles were measured during three repetitions of the restto-work transition of moderate aerobic square-wave exercise on nine healthy volunteers, while resting [PCr] was estimated from the appropriate spectroscopy data. PCr concentration decreased significantly (22 Ϯ 6%) from rest to steady-state exercise, without differences among the three repetitions. Absolute resting [PCr] and PCr were consistent with literature values, amounting to 27.5 Ϯ 2.2 mM and 23.9 Ϯ 2.9 s, respectively. No significant relationships were detected between individual PCr and mechanical power, fraction or absolute amount of PCr hydrolyzed, or change in ADP concentration. On the contrary, individual PCr (s) was linearly related to absolute resting [PCr] (mM), the relationship being described by: PCr ϭ 0.656 ϩ 0.841 ⅐ [PCr] (n ϭ 9, R ϭ 0.708, P Ͻ 0.05). These data support the view that in humans PCr concentration sets the time course of the oxidative metabolism in skeletal muscle at the start of exercise, being one of the main controllers of oxidative phosphorylation. mitochondrial respiration; 31 P-NMR spectroscopy; work onset AT THE ONSET of a square-wave moderate aerobic exercise, O 2 uptake (V O 2 ) increases at a slower rate than the (stepwise) increase in ATP utilization. However, ATP concentration in working muscles is maintained at a constant level (15,26) since the hydrolysis of phosphocreatine (PCr) fills the gap between energy requirement and energy yield by oxidative pathways. Thus, if no other energy sources are involved, e.g., in the absence of any detectable lactate production (8), at any time during the exercise the sum of the energy per unit of time derived from net oxygen consumption (V O 2 ) and from the PCr breakdown (V PCr) provides the overall required power (W). Under these conditions, both V O 2 and V PCr approach a new steady state in a complementary fashion since PCr represents a readily available source of energy that the muscle can use to cover the increased energy demand until oxidative metabolism meets the energy requirement. As a first approximation, after the onset of a constant-load exercise the time course of V O 2 and of PCr concentration ([PCr]) follow a first-order monoexponential kinetics, charact...