Parallel activation in the ATP supply–demand system lessens the impact of inborn enzyme deficiencies, inhibitors, poisons or substrate shortage on oxidative phosphorylation in vivo

Abstract

A potential kinetic impact of parallel activation of different steps during an increased energy demand on the effect of inborn enzyme deficiencies, physiological inhibitors, external poisons and substrate shortage on oxidative phosphorylation was studied in the theoretical way. Numerical simulations were performed with the aid of the previously developed computer model of oxidative phosphorylation. It was demonstrated that the parallel activation mechanism diminishes significantly changes in fluxes and metabolite concentrations occurring at a given degree of inactivation of the system by one of the above-mentioned factors. It was also shown that parallel activation decreases greatly the threshold value of the relative activity of oxidative phosphorylation, below which the oxygen consumption flux and ATP turnover flux become significantly affected. Finally, computer simulations predicted that parallel activation leads to a considerable increase in the apparent affinity of oxidative phosphorylation to oxygen, which delays the effect of inhibitors and poisons competing with oxygen for the active centre of cytochrome oxidase. It is concluded that one of possible functions of parallel direct activation of different steps of oxidative phosphorylation is to increase the resistance of the system to a decrease in the concentration/activity of different oxidative phosphorylation complexes.