Each-step activation of oxidative phosphorylation is necessary to explain muscle metabolic kinetic responses to exercise and recovery in XXXX .

@entity1 @entity2125 @entity1734 @entity908 @entity26 @entity855
KEY POINTS: The basic control mechanisms of oxidative phosphorylation (OXPHOS) and glycolysis during work transitions in @entity1 skeletal muscle are still a matter of debate. We used simulations of skeletal muscle bioenergetics to identify key system features that contribute to this debate, by comparing kinetic model outputs with experimental @entity1 data, including @entity1734 , pH, pulmonary @entity26 uptake and fluxes of @entity855 production by OXPHOS (vOX), anaerobic glycolysis and @entity908 kinase in moderate and severe intensity exercise transitions. We found that each-step activation of particular OXPHOS complexes, @entity2125 supply and glycolysis, and strong (third-order) glycolytic inhibition by protons was required to reproduce observed @entity1734 , pH and vOX kinetics during exercise. A slow decay of each-step activation during recovery, which was slowed further following severe exercise, was necessary to reproduce the experimental findings. Well-tested computer models offer new insight in the control of the @entity1 skeletal muscle bioenergetic system during physical exercise. ABSTRACT: To better understand muscle bioenergetic regulation, a previously-developed model of the skeletal muscle cell bioenergetic system was used to simulate the influence of: (1) each-step activation (ESA) of @entity2125 supply (including glycolysis) and oxidative phosphorylation (OXPHOS) complexes and (2) glycolytic inhibition by protons on the kinetics of @entity855 synthesis from OXPHOS, anaerobic glycolysis and @entity908 kinase. Simulations were fitted to previously published experimental data of @entity855 production fluxes and metabolite concentrations during moderate and severe intensity exercise transitions in bilateral knee extension in @entity1 . Overall, the computer simulations agreed well with experimental results. Specifically, a large (>5-fold) direct activation of all OXPHOS complexes was required to simulate measured @entity1734 and OXPHOS responses to both moderate and severe intensity exercise. In addition, slow decay of ESA was required to fit @entity1734 recovery kinetics, and the time constant of ESA decay was slower following severe (180  s) than moderate (90  s) exercise. Additionally, a strong inhibition of (anaerobic) glycolysis by protons (glycolytic rate inversely proportional to the cube of proton concentration) provided the best fit to the experimental pH kinetics, and may contribute to the progressive increase in oxidative @entity855 supply during acidifying contractions. During severe-intensity exercise, an 'additional' @entity855 usage (a 27% increase at 8  min, above the initial @entity855 supply) was necessary to explain the observed V  O2 slow component. Thus, parallel activation of @entity855 usage and @entity855 supply (ESA), and a strong inhibition of @entity855 supply by anaerobic glycolysis, were necessary to simulate the kinetics of muscle bioenergetics observed in @entity1 .
