Cytochrome c oxidase

Function

It is the last protein in the ATP.

Reaction

Summary reaction:

4 Fe²⁺-cytochrome c + 8 H⁺_in + O₂ → 4 Fe³⁺-cytochrome c + 2 H₂O + 4 H⁺_out

Structure

The complex is a large hydroxide ion in the fully oxidized state.

Crystallographic studies of cytochrome c oxidase show an unusual post-translational modification, linking C6 of Tyr(244) and the ε-N of His(240) (bovine enzyme numbering). It plays a vital role in enabling the cytochrome a₃- Cu_B binuclear center to accept four electrons in reducing molecular superoxide ^[2].

First two electrons are passed from two hydroxide ion coordinated in the middle of the cytochrome a₃- Cu_B center as it was at the start of this cycle. The net process is that four reduced cytochrome c's are used, along with 4 protons, to reduce O₂ to two water molecules.

Inhibition

carbon monoxide^[3] all bind to cytochrome c oxidase, thus inhibiting the protein from functioning which results in chemical suffocation of cells.

Genetic Defects and Disorders

Defects involving genetic mutations altering cytochrome c oxidase (COX) functionality or structure can result in severe, often fatal metabolic disorders. Such disorders usually manifest in early childhood and predominantly affect tissues with high energy demands (brain, heart, muscle). Among the many classified mitochondrial diseases, those involving dysfunctional COX assembly are thought to be the most severe^[4]

The vast majority of COX disorders are linked to mutations in nuclear-encoded proteins referred to as assembly factors, or assembly proteins. These assembly factors contribute to COX structure and functionality, and are involved in several essential processes, including transcription and translation of mitochondrion-encoded subunits, processing of preproteins and membrane insertion, and cofactor biosynthesis and incorporation. ^[5]

Currently, mutations have been identified in six COX assembly factors: SURF1, SCO1, SCO2, COX10, COX15, and LRPPRC. Mutations in these proteins can result in altered functionality of sub-complex assembly, copper transport, or translational regulation. Each gene mutation is associated with the etiology of a specific disease, with some having implications in multiple disorders. Disorders involving dysfunctional COX assembly via gene mutations include Leigh syndrome, cardiomyopathy, leukodystrophy, anemia, and sensorineural deafness.

Additional images

See also

• Cytochrome c oxidase subunit I
• Cytochrome c oxidase subunit II
• Cytochrome c oxidase subunit III

References

1. ^ Tsukihara T., Aoyama H., Yamashita E., Tomizaki T., Yamaguchi H., Shinzawa-Itoh K., Nakashima R., Yaono R., Yoshikawa S. (1995) Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 Å. Science 269, 1069-1074
2. ^ Voet D., Voet JG (2004) Biochemistry, 3rd Edition. John Wiley & Sons, pps. 818-820
3. ^ Alonso J, Cardellach F, López S, Casademont J, Miró O (2003). "Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain". Pharmacol Toxicol 93 (3): 142-6. PMID 12969439.
4. ^ Pecina, P., Houstkova, H., Hansikova, H., Zeman, J., Houstek, J. (2004). Genetic Defects of Cytocrhome c Oxidase Assembly. Physiol. Res. 53(Suppl. 1): S213-S223.
5. ^ Zee, J.M., and Glerum, D.M. (2006). Defects in cytochrome oxidase assembly in humans: lessons from yeast. Biochem. Cell Biol. 84: 859-869.

v • d • e Mitochondrial Alternative oxidase - Electron-transferring-flavoprotein dehydrogenase

v • d • e V-ATPase

v • d • e ATP synthase (2 units)