Q cycle

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History

The Q cycle describes a series of reactions first proposed by Peter Mitchell that describe how the sequential oxidation and reduction of the lipophilic electron carrier, ubiquinol-ubiquinone (a.k.a. Coenzyme Q), can result in the net pumping of protons across a lipid bilayer (in the case of mitochondria, the inner mitochondrial membrane). A modified version of Mitchell's original scheme is now accepted as the mechanism by which Complex III pumps protons (i.e. how biochemical generation of ATP is achieved).

Process

Operation of the modified Q cycle in Complex III results in the oxidation of Cytochrome c, reduction of ubiquinol to ubiquinone, and the transfer of four protons into the intermembrane space, per two-cycle process.

Ubiquinol (QH₂) binds to the Q_o site of complex III via hydrogen bonding to His181 of the Rieske iron-sulfur protein His181 and Glu272 of Cytochrome b. Ubiquinone (Q), in turn, binds the Q_i site of complex III. Ubiquinol is divergently oxidized (gives up one electron each) to the Rieske iron-sulfur '(FeS) protein' and to the b_L heme. This oxidation reaction produces a transient semiquinone before complete oxidation to ubiquinone, which then leaves the Q_o site of complex III.

Having acquired one electron from ubiquinol, the 'FeS protein' is freed from its electron donor and is able to migrate to the Cytochrome c₁ subunit. 'FeS protein' then donates its electron to Cytochrome c₁, reducing its bound heme group^[1][2]. The electron is from there transferred to an oxidized molecule of Cytochrome c externally bound to complex III, which then dissociates from the complex. In addition, the reoxidation of the 'FeS protein' releases the proton bound to His181 into the intermembrane space.

The other electron, which was transferred to the b_L heme, is used to reduce the b_H heme, which in turn transfers the electron to the ubiquinone bound at the Q_i site. The attached ubiquinone is thus reduced to a semiquinone radical. The proton taken up by Glu272 is subsequently transferred to a hydrogen-bonded water chain as Glu272 rotates 170° to hydrogen bond a water molecule, in turn hydrogen-bonded to a propionate of the b_L heme^[3].

Because the last step leaves a stable semiquinone at the Q_i site, the reaction is not yet fully completed. A second Q cycle is necessary, with the second electron transfer from cytochrome b_H reducing the semiquinone to ubiquinol. The ultimate products of the Q cycle are four protons entering the intermembrane space, two protons taken up from the matrix and the reduction of two molecules of cytochrome c. The reduced cytochrome c is eventually reoxidized by complex IV. The process is cyclic as the ubiquinone created at the Q_i site can be reused by binding to the Q_o site of complex III.

Notes

1. ^ Zhang, Z., Huang, L., Schulmeister, V.M., Chi, Y.I., Kim, K.K., Hung, L.W., Crofts, A.R., Berry, E.A. and Kim, S.H. (1998) Nature 392, 677-684.
2. ^ Crofts, A.R., Hong, S., Ugulava, N., Barquera, B., Gennis, R., Guerrgova-Kuras, M. and Berry, E. (1999) Proc. Natl. Acad. Sci. USA 96, 10021-10026.
3. ^ Palsdottir, H., Gomez-Lojero, Trumpower, B.L. and Hunte, C. (2003) J. Biol. Chem., 31303-31311

References and Reviews

• Trumpower, B.L. (2002) Biochim. Biophys. Acta 1555, 166-173

• Hunte, C., Palsdottir, H. and Trumpower, B.L. (2003) FEBS Letters 545, 39-46
• Trumpower, B.L. (1990) J. Biol. Chem., 11409-11412