Regulation of metabolism: the rest-to-work transition in skeletal muscle

Am J Physiol Endocrinol Metab. 2015 Nov 1;309(9):E793-801. doi: 10.1152/ajpendo.00355.2015. Epub 2015 Sep 22.


Mitochondrial oxidative phosphorylation is programmed to set and maintain metabolic homeostasis, and understanding that program is essential for an integrated view of cellular and tissue metabolism. The behavior predicted by a mechanism-based model for oxidative phosphorylation is compared with that experimentally measured for skeletal muscle when work is initiated. For the model, initiation of work is simulated by imposing a rate of ATP utilization of either 0.6 (equivalent of 13.4 ml O2·100 g tissue(-1)·min(-1) or 6 μmol O2·g tissue(-1)·min(-1)) or 0.3 mM ATP/s. Creatine phosphate ([CrP]) decrease, both experimentally measured and predicted by the model, can be fit to a single exponential. Increase in ATP synthesis begins immediately but can show a "lag period," during which the rate accelerates. The length of the lag period is similar for both experiment and model; in the model, the lag depends on intramitochondrial [NAD(+)]/[NADH], mitochondrial content, and size of the creatine pool ([CrP] + [Cr]) as well as the resting [CrP]/[Cr]. For in vivo conditions, increase in oxygen consumption may be linearly correlated with a decrease in [CrP] and an increase in inorganic phosphate ([Pi]) and [Cr]. The decrease in [CrP], resting and working steady state [CrP], and the increase in oxygen consumption are dependent on the Po2 in the inspired gas (experimental) or tissue Po2 (model). The metabolic behavior predicted by the model is consistent with available experimental measurements in muscle upon initiation of work, with the model providing valuable insight into how metabolic homeostasis is set and maintained.

Keywords: metabolic control; metabolic homeostasis; muscle work; rest-to-work transition; skeletal muscle.

MeSH terms

  • Animals
  • Basal Metabolism
  • Computer Simulation
  • Creatine / metabolism
  • Energy Metabolism / physiology*
  • Homeostasis
  • Mitochondria, Muscle / metabolism*
  • Models, Biological
  • Motor Activity / physiology
  • Muscle, Skeletal / metabolism*
  • Oxidative Phosphorylation
  • Oxygen / metabolism
  • Oxygen Consumption / physiology
  • Rats
  • Rest / physiology*


  • Creatine
  • Oxygen