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Oxidative ATP Synthesis in Skeletal Muscle is Controlled by Substrate Feedback

Model Behavior and Validation

Model prediction of ADP concentration and inorganic phosphate concentration in cytoplasm against ATP hydrolysis rate in the healthy subjects. (A.) Plot of predicted ADP concentration in cytoplasm, [ADP]_c, as a function of ATP hydrolysis rate, ATPase flux. (B.) Plot of predicted inorganic phosphate concentration in cytoplasm, [Pi]_c, as a function of ATP hydrolysis rate, ATPase flux. The solid line represents model-predicted results. The circle points represent experimentally-measured estimation from Jeneson et al. (9)

 

Model prediction of ADP concentration and inorganic phosphate concentration in cytoplasm against ATP hydrolysis rate in the complex I deficient subjects. (A.) Plot of predicted ADP concentration in cytoplasm as a function of ATP hydrolysis rate, ATPase flux. (B.) Plot of predicted inorganic phosphate concentration in cytoplasm as a function of ATP hydrolysis rate, ATPase flux. The solid line represents model-predicted results. The circle points represent experimentally-measured estimation from Jeneson et al. (8)

 

Model prediction of ADP concentration and inorganic phosphate concentration in cytoplasm against ATP hydrolysis rate in the ANT deficient subjects. (A.) Plot of predicted ADP concentration in cytoplasm as a function of ATP hydrolysis rate, ATPase flux. (B.) Plot of predicted inorganic phosphate concentration in cytoplasm as a function of ATP hydrolysis rate, ATPase flux. The solid line represents model-predicted results. The circle points represent experimentally-measured estimation from Bakker et al. (3)

 

Model-generated curves of free energy of ATP hydrolysis against ATP hydrolysis rate for the healthy subjects, the complex I deficient subjects, and the ANT deficient subjects. The free energy of ATP hydrolysis DGATP, is computed based on model-predicted concentrations of metabolites in cytoplasm. The dashed line corresponds to a DGATP value of -55 kJ/mole.