Analyzing the Functional Properties of the Creatine Kinase System with Multiscale ‘Sloppy’ Modeling
Figure 6
Fluctuations of metabolite concentrations and fluxes during the cardiac cycle at three levels of CK activity.
Plots show (A–C) Trajectory of the forcing function of ATP hydrolysis and ensemble predictions of (D–F) Rdiff,PCr, (G–I) mitochondrial ATP synthesis rate, (J–L) cytosolic ADP and (M–O) cytosolic Pi concentrations at heart rate 220 bpm. Mi-CK and MM-CK activities were set to 2, 100, and 300% of wildtype levels. Three cardiac cycles are shown at steady state. Solid lines show the simulated trajectory of the optimized parameter set (see Table 1). Shaded regions show the 95% confidence interval for all trajectories of the ensemble of 658 parameter sets. To alter CK activity, the parameters describing maximum enzyme velocity, Vmax,Mif and Vmax,MMf, are changed in parallel to the indicated percentage.