CHAPTER 14: Oxygen Reduction and Proton Translocation by Respiratory Cytochrome c Oxidase

Cell respiration is mainly catalysed by the so-called heme–copper oxygen reductases, which are characterised by a binuclear active site containing an oxygen-binding heme group and a nearby copper ion. The copper ion is ligated by three histidine residues, one of which is covalently bonded to a tyrosine residue and takes active part in the reduction of O₂ to water. In addition, a low-spin heme is located adjacent to the oxygen-binding heme serving as the immediate electron donor to the binuclear site. Binding of O₂ is followed by a “concerted” four-electron reduction confined within the binuclear site, leaving the site in a highly oxidised configuration, akin to the classical Compound I of the peroxidases and catalase. The catalytic cycle is then completed by sequential additions of four electrons to the binuclear centre, one at a time, to end up in the initial reduced state that binds the next O₂. These four electron transfers are intimately coupled to proton translocation across the mitochondrial (or bacterial) membrane, which gives the function of the heme–copper oxygen reductases an additional intriguing dimension.