Regulation of cytochrome oxidase: theoretical studies

Using the dynamic model of oxidative phosphorylation developed previously and tested for its validity under a broad range of conditions some properties of cytochrome oxidase in the whole system considered were simulated. The regulation of this enzyme by oxygen concentration, delta p and reduction level of cytochrome c were studied. Assuming at least qualitative validity of the model, the following conclusions were drawn: (1) Regulation of cytochrome oxidase is different under the same conditions, when changes in the system (oxidative phosphorylation in isolated mitochondria) are imposed by a decrease in oxygen concentration (aerobiosis-->anaerobiosis transition) or by addition of hexokinase (state 4-->state 3 transition). In the former case, cytochrome c and delta p play a very similar role in the compensation for a decrease in the respiration rate caused by lowered oxygen concentration, while in the latter case changes in delta p activate cytochrome oxidase much stronger than changes in the reduction level of cytochrome c. (2) There is no unique thermodynamic flux-force relationship for cytochrome oxidase. This relationship depends on how the thermodynamic span of the reaction catalyzed by this enzyme is changed (aerobiosis-->anaerobiosis transition vs. state 4-->state 3 transition). (3) Under some conditions (aerobiosis-->anaerobiosis transition) the flux-force relationship can be inverse, i.e. increase in a thermodynamic force occurs simultaneously with decrease in a reaction rate.