| In aerobic life, the protein cytochrome c oxidase (CcO) is responsible for the conversion of chemical energy from food into the electrochemical gradient that powers the synthesis of ATP. As the terminal enzyme of the respiratory chain, CcO reduces oxygen to water and uses the released energy to pump protons across a membrane. In my talk I will describe how the chemical energy of oxygen reduction is used to move protons against an electrochemical gradient without violation of the second law of thermodynamics. We have constructed models consistent with thermodynamic principles, the structure of CcO, experimentally known proton affinities, and equilibrium constants of intermediate reactions. The resulting models are found to capture key properties of CcO, including the midpoint redox potentials of the metal centers and the electron transfer rates. The high pumping efficiency of these models requires strong electrostatic couplings between the proton loading (pump) site and the electron site (heme a), and kinetic gating of the internal proton transfer. The fundamental mechanisms identified here for the efficient conversion of chemical energy into an electrochemical potential should prove relevant also for other molecular machines and novel fuel cell designs. |
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