title: Regulation of metabolism: the work-to-rest transition in skeletal muscle.
abstract: The behavior of oxidative phosphorylation predicted by a model for the mechanism and kinetics of cytochrome c oxidase is compared with the experimentally observed behavior during the work-to-rest transition in skeletal muscle. For both experiment and model, when work stops, the increase in creatine phosphate and decrease in creatine and inorganic phosphate concentrations ([CrP], [Cr], and [Pi]) begin immediately. The rate of change for each is maximal and then progressively slows as the increasing energy state ([ATP]/[ADP][Pi]) suppresses the rate of oxidative phosphorylation. The time courses can be reasonably fitted to single exponential curves with similar time constants. The energy state in the working and resting steady states at constant Po2are dependent on the intramitochondrial [NAD+]/[NADH], mitochondrial content, and size of the creatine pool ([CrP] + [Cr]). The rate of change in [CrP] is linearly correlated with [CrP] and with [Pi] and [Cr]. The time constant for [CrP] increase in the resting and working steady states, and the rate of decrease in oxygen consumption are similarly dependent on the Po2in the inspired gas (experimental) or tissue Po2(model). Myoglobin strongly buffers intracellular Po2below ∼15 torr, truncating the low end of the oxygen distribution in the tissue and suppressing intra- and intermyocyte oxygen gradients. The predictions of the model are consistent with the experimental data throughout the work/rest transition, providing valuable insights into the regulation of cellular and tissue metabolism.
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania wilsondf@mail.med.upenn.edu.
authors.forename: David F
authors.initials: DF
authors.lastname: Wilson
mesh_terms: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003401:Creatine; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism*; D012146:Rest
chemical_list: D009211:Myoglobin; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D003401:Creatine; D010100:Oxygen
keywords: energy metabolism; exercise; metabolic control; metabolic homeostasis; oxidative phosphorylation; oxygen consumption; respiration