Cytochrome Oxidase at the Membrane/Water Interface: Mechanism of Functioning and Molecular Recognition

Abstract

A concerted 2:1:1-electron mechanism for cytochrome oxidase functioning is evaluated by thermodynamic and kinetic analysis. Possible ways of dioxygen reduction to water as well as the stoichiometry of the proton pump are analyzed thermodynamically. The conditions are formulated for the occurrence of multielectron oxygen reduction. Kharkats and Volkov first presented proofs that cytochrome c oxidase reduces molecular oxygen by synchronous multielectron mechanism without O₂^- intermediate formation (Yu. I. Kharkats and A. G. Volkov, Biochim. Biophys. Acta, 891, 56 (1987)). As the field progresses after this pioneering observations, it became clear that the first step of dioxygen reduction is two-electron concerted process. As follows from thermodynamics energy for the H⁺-pump functioning is liberated only at the last two steps of water formation on addition of third and fourth electrons independently of the reaction pathway. The media reorganization energy corresponding to simultaneous electrons and protons transfer will be minimal in the case then the directions of their transfers are close. In mitochondrial cytochrome c oxidase the donor of electrons is placed on the side C and the protons comes from the side M. In this case the minimal activation energy will be achieved at maximal possible at given geometry of the system angle between the directions of electrons and protons transfer.