Electron and Proton Transfer in Heme-Copper Oxidases

In eukaryotes, the process of energy transduction coupled to electron transfer occurs in mitochondria, where cytochrome c oxidase catalyzes the transfer of electrons derived from foodstuffs to oxygen, the final electron sink. The reduction of oxygen to water and the concomitant translocation of protons are carried out by a member of a family of enzymes: the heme-copper oxidases (Saraste, 1990; Garcia-Horsman et al., 1994). A number of these oxidases have now been identified in bacterial systems; all use a heme-copper center to carry out the oxygen chemistry, but not all have similar auxiliary metal centers. The eu karyotic and some prokaryotic enzymes contain an additional heme a, an additional bimetallic copper center, and a magnesium ion. These oxidases use cytochrome c as their immediate electron donor. Another group of oxidases in the family use quinol as a substrate and contain neither an extra copper center nor magnesium. Although the two groups are likely to have similar energy transduction mechanisms, this discussion will focus on the cytochrome c oxidases with the additional copper and magnesium and on our efforts to define the roles of these auxiliary metals in controlling electron input, proton output, and coupling efficiency.