Bistability in fatty-acid oxidation resulting from substrate inhibition
Fig 2
Bistability and hysteresis in mitochondrial fatty acid oxidation.
The simulated steady state of mFAO uptake fluxes for increasing and decreasing palmitoyl-CoA concentrations are based on the rat liver model [20] with the [NAD+]: [NADH] ratio equal to 20 and all other parameters unchanged. A. Steady state uptake flux of palmitoyl-CoA for increasing (red curve) and decreasing (blue curve) palmitoyl-CoA concentrations. The arrows indicate in which direction the palmitoyl-CoA concentration was varied. B. The real parts of the eigenvalues of the Jacobian matrix plotted against the palmitoyl-CoA concentration. The bistable region between the critical points is characterized by two stable steady states, as can be inferred from their eigenvalues. C. Time course solution until convergence to a stable state starting from initial states close to the unstable stable. Cytosolic palmitoyl-CoA 120 μM, initial mitochondrial palmitoyl-CoA 13.41 (red) or 15.41 μM (blue). D. Steady-state mitochondrial against cytosolic palmitoyl-CoA; the light-blue line denotes the unstable state, and red and dark-blue lines, respectively the low- and high-flux state.