Simulation of oxidative phosphorylation in hepatocytes

The dynamic mathematical model of oxidative phosphorylation proposed previously was modified, developed and further tested. The description of cytochrome oxidase kinetics was changed to involve dependence on Deltap. Simple, phenomenological descriptions of the kinetics of substrate dehydrogenation and ATP usage, able to reflect experimental data correctly, were found. The kinetic response of the oxidation subsystem (substrate dehydrogenation, respiratory chain), phosphorylation subsystem (ATP synthase, ATP/ADP carrier, phosphate carrier, ATP usage) and proton leak to the changes of Deltap in isolated hepatocytes incubated with different respiratory substrates was simulated. The simulations revealed a good agreement with the experimental results. Simple, intuitive assumptions were able, when introduced into the model, to explain differences in the properties of the oxidative phosphorylation system working with different respiratory substrates. It was proposed, therefore, that our explicit understanding of the oxidative phosphorylation system was good enough to explain many properties of this system correctly, at least in the range of physiological conditions tested.