Coenzyme Q - cytochrome c reductase
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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), playing a critical role in biochemical generation of ATP (oxidative phosphorylation). Complex III is a multisubunit transmembrane lipoprotein encoded by both the mitochondrial (cytochrome b) and the nuclear genomes (all other subunits). Complex III is present in the mitochondria of all animals and all aerobic eukaryotes and the inner membranes of most eubacteria. Mutations in Complex III cause exercise intolerance as well as multisystem disorders.
Reaction
It catalyzes the reduction of cytochrome c by oxidation of coenzyme Q (CoQ) and the concomitant pumping of 4 protons from the mitochondrial matrix to the intermembrane space:
- QH2 + 2 cytochrome c (FeIII) + 2 H+in → Q + 2 cytochrome c (FeII) + 4 H+out
In the process called Q cycle,[1][1] 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.
Structure
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 eleven subunits are found in higher animals [1]. Three subunits have prosthetic groups. The cytochrome b subunit has two b-type hemes (bL and bH), the cytochrome c sununit has one c-type heme (c1), and the Rieske Iron Sulfur Protein subunit (ISP) has a two iron, two sulfur iron-sulfur cluster (2Fe•2S).
Structures of complex III: PDB 1KYO, PDB 1L0L
Inhibitors of complex III
There are three distinct groups of Complex III inhibitors.
- Antimycin A binds to the Qi site and inhibits the transfer of electrons in Complex III from heme bH to oxidized Q (Qi site inhibitor).
- Myxothiazol and stigmatellin binds to the Qo site and inhibits the transfer of electrons from reduced QH2 to the Rieske Iron sulfur protein. Myxothiazol and stigmatellin bind to distinct pockets within the Qo site.
- Myxothiazol binds very close to cytochrome bL (hence termed a "proximal" inhibitor).
- 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).
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 otherwise 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 (the free radical theory of aging). Electron leakage occurs mainly at the Qo site and is stimulated by antimycin A. Antimycin A locks the b hemes in the reduced state by preventing their re-oxidation at the Qi site, which in turn causes the steady state concentrations of the Qo 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 [1]. Superoxide produced at the Qo site can be released both into the mitochondrial matrix [1][1] and intermembrane space (from where it can reach the cytosol [1][1]). This could be explained by the fact that Complex III might produce superoxide as membrane permeable HO2 rather than as membrane impermeable O2- [1].
References
See also
Additional images
 ETC |
 ETC |
External links
- cytochrome bc1 complex site (Edward A. Berry) at lbl.gov
- cytochrome bc1 complex site (Antony R. Crofts) at uiuc.edu
- PROMISE Database: cytochrome bc1 complex at scripps.edu
- Interactive Molecular Model of Complex III (Requires MDL Chime)
- UMich Orientation of Proteins in Membranes families/superfamily-3 - Calculated positions of bc1 and related complexes in membranes
- MeSH Coenzyme+Q-Cytochrome-c+Reductase
Diphenol family oxidoreductases (EC 1.10) |
|---|
| Coenzyme Q - cytochrome c reductase - Catechol oxidase - Laccase - Alternative oxidase |
Mitochondrial electron transport chain/oxidative phosphorylation | |
|---|---|
| Primary | Complex I/NADH dehydrogenase - Complex II/Succinate dehydrogenase - Coenzyme Q - Complex III/Coenzyme Q - cytochrome c reductase - Cytochrome c - Complex IV/Cytochrome c oxidase |
| Other | Alternative oxidase - Electron-transferring-flavoprotein dehydrogenase |
Ion pump: proton pumps | |
|---|---|
| ETC | ETC Complex I - ETC Complex III - ETC Complex IV |
| Other | Bacteriorhodopsin - Cytochrome b6f complex - Inorganic pyrophosphatase - V-ATPase |
fr:Coenzyme Q - cytochrome c-réductase it:Ubiquinolo-citocromo c reduttasi
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
