TheQ cycle (named forquinol) describes a series of sequential oxidation and reduction of the lipophilic electron carrierCoenzyme Q (CoQ) between theubiquinol andubiquinone forms. These reactions can result in the net movement ofprotons across alipidbilayer (in the case of the mitochondria, the innermitochondrial membrane).
The Q cycle was first proposed byPeter D. Mitchell, though a modified version of Mitchell's original scheme is now accepted as the mechanism by which Complex III moves protons (i.e. howcomplex III contributes to the biochemical generation of the proton or pH, gradient, which is used for the biochemical generation ofATP).
The first reaction of Q cycle is the 2-electron oxidation of ubiquinol by two oxidants,c1 (Fe3+) and ubiquinone:
The second reaction of the cycle involves the 2-electron oxidation of a second ubiquinol by two oxidants, a freshc1 (Fe3+) and the CoQ'−• produced in the first step:
These net reactions are mediated by electron-transfer mediators including a Rieske 2Fe-2S cluster (shunt toc1) andcb (shunt to CoQ' and later to CoQ'−•)
In chloroplasts, a similar reaction is done withplastoquinone bycytochrome b6f complex.
Operation of the modified Q cycle inComplex III results in the reduction ofCytochrome c, oxidation ofubiquinol toubiquinone, and the transfer of four protons into the intermembrane space, per two-cycle process.
Ubiquinol (QH2) binds to the Qo site ofcomplex III viahydrogen bonding to His182 of theRieske iron-sulfur protein and Glu272 ofCytochrome b. Ubiquinone (Q), in turn, binds the Qi site of complex III. Ubiquinol is divergently oxidized (gives up one electron each) to theRieske iron-sulfur '(FeS) protein' and to thebLheme. This oxidation reaction produces a transient semiquinone before complete oxidation to ubiquinone, which then leaves the Qo 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 ofCytochrome 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 thebL heme, is used to reduce thebH heme, which in turn transfers the electron to the ubiquinone bound at the Qi site. The movement of this electron is energetically unfavourable, as the electron is moving towards the negatively charged side of the membrane. This is offset by a favourable change in EM from −100 mV in BL to +50mV in the BH heme.[citation needed] The attached ubiquinone is thus reduced to asemiquinone 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 apropionate of thebL heme.[3]
Because the last step leaves an unstablesemiquinone at the Qi site, the reaction is not yet fully completed. A second Q cycle is necessary, with the second electron transfer from cytochromebH reducing the semiquinone to ubiquinol. The ultimate products of the Q cycle are four protons entering the intermembrane space, two from the matrix and two from the reduction of two molecules of cytochrome c. The reduced cytochrome c is eventually reoxidized bycomplex IV. The process is cyclic as the ubiquinol created at the Qi site can be reused by binding to the Qo site of complex III.