Cytochrome c Oxidase


Cytochrome c oxidase is the key enzyme of cell respiration in all eukaryotes and many prokaryotes. The cytochrome c oxidases belong to the haem–copper superfamily of structurally and functionally related enzymes; though related in structure, some bacterial variants lack amino acid residues that are known to be obligatory for the function of the members of the main family. All haem–copper oxidases have a unique bimetallic active site catalysing reduction of dioxygen (O2) to water and an adjacent second haem group that donates electrons to this site. Here, the mechanism of O2 reduction is reviewed. The membrane‐bound enzyme couples this reaction to translocation of protons across the membrane, and thus functions as a primary energy transducer that contributes to the formation of ATP (adenosine triphosphate) in aerobic life. The most recent knowledge of the function of this ‘proton pump’ is discussed. It is concluded that cytochrome c oxidase is an electrostatic energy‐transducing machine with high efficiency.

Key Concepts:

  • Cytochrome c oxidase is an electrostatically coupled energy transducer.

  • The high affinity for O2 is due to kinetic ligand trapping.

  • O2 reduction in cell respiration yields no reactive oxygen species.

Keywords: cell respiration; haem–copper oxidases; respiratory chain; ATP synthesis; transmembrane protein; proton translocation; energy transduction; electron transfer; oxygen reduction

Figure 1.

(a) Stereo view of the transmembrane helix backbone arrangement of subunit I from the outside, perpendicular to the membrane. Transmembrane helices are numbered I–XII, and they form ‘pores’ denoted A, B and C. Haems a and a3 are shown in pores C and B, respectively. (b) Stereo view of the backbone of subunit II in the membrane plane, showing the binuclear CuA site and its relationship to the two haem groups in subunit I. (c) Top view similar to that in (a) of the backbone of subunit III (highlighted) relative to subunit I with the two haem groups. (d) Side view of C along the membrane plane. Notice the V shape with two transmembrane helices in one leg (left) and five in the other (right). These pictures are based on the crystal structure of cytochrome c oxidase from bovine heart mitochondria (Tsukihara et al., ; Brookhaven protein data bank, accession number 1OCC).

Figure 2.

(a) Schematic view of the functioning of cytochrome c oxidase as a generator of . Protons consumed in the reduction of dioxygen to water are shown in blue and protons translocated in red. Electron transfer is shown in light blue. (b) The binuclear O2‐binding centre. The fourth water or OH ligand of CuB, which has been identified by EXAFS and ENDOR spectroscopy, is not shown.

Figure 3.

States of the binuclear oxygen reduction site during the catalytic cycle. The rectangle shows the active site with haem a3, CuB and the cross‐linked Tyr‐244. The proximal histidine ligand of the haem and the three histidine ligands of CuB are not shown for simplicity. Red arrows indicate steps coupled to proton translocation. Black H+ indicates uptake of a ‘substrate proton’ forming the equivalent of water.

Figure 4.

Pathways of proton uptake. The backbones of subunits I (green) and II (silver) are shown in a phospholipid membrane. The P‐ and N‐sides indicate the positively and negatively charged sides, respectively. Subunit I includes the heme groups a (left) and a3 (right) drawn in purple, and a nonpolar cavity (in yellow) above the residue Glu242 (E242). Two proton uptake pathways are indicated by red arrows. The D‐pathway (left) starts with Asp91 (D91) and ends at Glu242. The K‐pathway is named after the conserved residue Lys319 (K319) and ends at Tyr244 (not shown) near heme a3.



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Further Reading

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How to Cite close
Wikström, Mårten(May 2010) Cytochrome c Oxidase. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000649.pub2]