Coenzyme Q - cytochrome c reductase

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schematic illustration of complex III reactions

The coenzyme Q : cytochrome c — oxidoreductase, sometimes called the cytochrome bc₁ complex, and at other times complex III, is the third complex in the electron transport chain (EC 1.10.2.2). It is a transmembrane lipoprotein, and it catalyzes the reduction of cytochrome c by oxidation of coenzyme Q (CoQ):

QH₂ + 2 cytochrome c (Fe^III) + 2 H⁺_in → Q + 2 cytochrome c (Fe^II) + 4 H⁺_out

In the process called Q cycle,^[1]^[2] two protons are consumed from the matrix (M), four protons are released into the inter membrane space (IM) and two electrons are passed to cytochrome c.

1 Structure
2 Inhibitors of complex III
3 Oxygen free radicals
4 References
5 See also
6 Additional images
7 External links

[edit] Structure

structure of complex III

Compared to the other major proton pumping subunits of the electron transport chain, the number of subunits found can be small, as small as three polypeptide chains. This number does increase, and as many as eleven subunits can be found in higher animals. The prosthetic groups in the complex are a pair of heme b (b_L and b_H), one heme c (c₁), and a two iron, two sulfur iron-sulfur cluster (2Fe•2S).

Structures of complex III: PDB 1KYO, PDB 1L0L

[edit] Inhibitors of complex III

There are three distinct groups of Complex III inhibitors. Antimycin A binds to the Q_i site and inhibits the transfer of electrons in Complex III from heme b_H to oxidized Q (Qi site inhibitor). Myxothiazol and stigmatellin binds to the Q_o site und inhibits the transfer of electrons from reduced QH₂ to the Rieske Iron sulfur protein. Myxothiazol and stigmatellin bind to distinct pockets within the Q_o site. Myxothiazol binds very close to cytochrome bL (hence termed a "proximal" inhibitor while Stigmatellin binds near the Rieske Iron sulfur protein, with which it strongly interacts.

Some have been commercialized as fungicides (the strobilurin derivates) and as anti-malaria agents (atovaquone).

[edit] Oxygen free radicals

A small fraction of electrons leave the electron transport chain before reaching complex IV. Premature electron leakage to oxygen results in the formation of superoxide. The relevance of this otheriwse minor side reaction is that superoxide and other reactive oxygen species are highly toxic and are thought to play a role in several pathologies, including aging. Electron leakage occurs mainly at the Q_o site and is stimulated by antimycin A. Antimycin A locks the b hemes in the reduced state by preventing their re-oxidation at the Q_i site, which in turn causes the steady state concentrations of the Q_o semiquinone to rise, the latter species reacting with oxygen to form superoxide. The effect of high membrane potential is thought to have a similar effect.

[edit] References

^ Kramer, D. M.; Roberts, A. G.; Muller, F.; Cape, J.; Bowman, M. K. Q-cycle bypass reactions at the Qo site of the cytochrome bc1 (and related) complexes. Methods Enzymol. 382:21-45; 2004. PMID 15047094
^ Crofts, A.R. (2004). The cytochrome bc1 complex: function in the context of structure. Annu Rev Physiol. 66, 689-733. PMID 14977419