Electron transfer from reduced cytochrome c to molecular oxygen

Stable Identifier
R-HSA-163214
Type
Reaction [transition]
Species
Homo sapiens
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Complex IV (COX, cytochrome c oxidase) contains the hemeprotein cytochrome a and a3. It also contains copper atoms which undergo a transition from Cu+ to Cu2+ during the transfer of electrons through the complex to molecular oxygen. A bimetallic centre containing a copper atom and a heme-linked iron protein binds oxygen after 4 electrons have been picked up. Water, the final product of oxygen reduction, is then released. Oxygen is the final electron acceptor in the respiratory chain. The overall reaction can be summed as

4Cyt c (red.) + 12H+ (in) + O2 = 4Cyt c (ox.) + 2H2O + 8H+ (out)

Four protons are taken up from the matrix side of the membrane to form the water (scalar protons). Wikstrom (1977) suggests 4 protons are additionally transferred out from the matrix to the intermembrane space.

COX ancillary proteins mediate membrane insertion, catalytic core processing, copper transport and insertion into core subunits and heme A biosynthesis (Stilburek et al. 2006, Fontanesi et al. 2006, Soto et al. 2012). To date, all Mendelian disorders presenting COX deficiency have been assigned to mutations in ancillary factors, with the exception of an infantile encephalomyopathy caused by a defective COX6B1 and an exocrine pancreatic insufficiency caused by a defective COX4I2 gene (Soto et al. 2012). Balsa et al have shown that NDUFA4, formerly considered to be a constituent of NADH dehydrogenase (Complex I), is instead a component of the cytochrome c oxidase (CIV) (Balsa et al. 2012). Patients with NDUFA4 mutations display COX deficiencies (Pitceathly et al. 2013).

Literature References
PubMed ID Title Journal Year
17298220 Biogenesis of eukaryotic cytochrome c oxidase

Stiburek, L, Hansikova, H, Tesarova, M, Cerna, L, Zeman, J

Physiol Res 2006
21958598 Biogenesis and assembly of eukaryotic cytochrome c oxidase catalytic core

Soto, IC, Fontanesi, F, Liu, J, Barrientos, A

Biochim. Biophys. Acta 2012
7979252 Energy transduction by cytochrome complexes in mitochondrial and bacterial

Trumpower, BL, Gennis, RB

Annu Rev Biochem 1994
15223 Proton pump coupled to cytochrome c oxidase in mitochondria

Wikstrom, MK

Nature 1977
22902835 NDUFA4 is a subunit of complex IV of the mammalian electron transport chain

Balsa, E, Marco, R, Perales-Clemente, E, Szklarczyk, R, Calvo, E, Landázuri, MO, Enríquez, JA

Cell Metab. 2012
23746447 NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease

Pitceathly, RD, Rahman, S, Wedatilake, Y, Polke, JM, Cirak, S, Foley, AR, Sailer, A, Hurles, ME, Stalker, J, Hargreaves, I, Woodward, CE, Sweeney, MG, Muntoni, F, Houlden, H, Taanman, JW, Hanna, MG

Cell Rep 2013
16760263 Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular process

Fontanesi, F, Soto, IC, Horn, D, Barrientos, A

Am. J. Physiol., Cell Physiol. 2006
11340051 Structures and proton-pumping strategies of mitochondrial respiratory

Schultz, BE, Chan, SI

Annu Rev Biophys Biomol Struct 2001
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Catalyst Activity
Title
cytochrome-c oxidase activity of Cytochrome c oxidase [mitochondrial inner membrane]
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