512—Energetics of the chemical coupling between ATP production and oxygen reduction: Comparison with electrochemical data

The chemiosmotic coupling hypothesis of the mechanism of mitochondrial oxidative phosphorylations implies that molecular oxygen is reversibly reduced by four electrons at a time directly to water at potentials near equilibrium values for this redox couple.Since many experimental data show that this is certainly not the case, at least one and probably two ATP per exchanged pair electron must be derived from another kind of coupling mechanism.If one assumes that all intermolecular electron transfers involving more than two electrons at a time and/or any kind of change of covalent topology of relatively heavy atoms are kinetically forbidden, it appears that in fact oxygen must be primarily reduced by the electron-transfer chain to hydrogen peroxide near equilibrium potentials of the O₂(g)|H₂O₂ redox couple. This production of hydrogen peroxide is followed more slowly by its disproportionation.An energetic analysis of the mechanism of this disproportionation, taking into account the proposed kinetic forbidding rule, leads to the conclusion that the production of one or two ATP must be coupled by this catalytic process. Possible coupling enzymes and artificial coupling disproportionation catalysts can be a priori defined by a few functional characteristics.