Proton-motive Q cycle

The proton-motive Q-cycle model, put forward by Mitchell (references 80 and 81) and by Trumpower and co-workers, is invoked in the following manner (1) One electron is transferred from ubiquinol (ubiquinol oxidized to ubisemi-quinone see Figure 7.27) to the Rieske [2Fe-2S] center at the Qo site, the site nearest the intermembrane space or p side (2) this electron can leave the bci complex via an attached cytochrome c or be transferred to cytochrome Ci (3) the reactive ubisemiquinone reduces the low-potential heme bL located closer to the membrane s intermembrane (p) side (4) reduced heme bL quickly transfers an electron to high-potential heme bn near the membrane s matrix side and (5) ubiquinone or ubisemiquinone oxidizes the reduced bn at the Qi site nearest the matrix or n side. Proton translocation results from the deprotonation of ubiquinol at the Qo site and protonation of ubisemiquinone at the Qi site. Ubiquinol generated at the Qi site is reoxidized at the Qo site (see Figure 7.27). Additional protons are transported across the membrane from the matrix (see Figure 7.26 illustrating a similar process for cytochrome b(6)f). The overall reaction can be written... 

This has been one of the most controversial areas of bioenergetics and is concerned with the role of coenzyme Q. The simplest view of the role of this coenzyme is that it acts as a mobile (2H+ + 2e ) carrier, linking complexes I and II with complex III. However, coenzyme Q may be involved in (H+ + e ) transfer within complex III. One model for this is the proton-motive Q cycle (Fig. 14-6), developed by Mitchell in 1975. This model satisfies prediction (2) of Example 14.10, in that coenzyme Q acts as an (H+ +e ) carrier in two loops. In this model, reduced coenzyme Q (QH2) is linked to oxidized coenzyme Q (Q) via the free-radical semiquinone (QH-) This model provides an explanation for the H+/e stoichiometry. 

The coupling of electron transfer and proton translocation is described by the proton-motive Q-cycle mechanism first proposed by Peter Mitchell [1], In the bc complex, hydroquinone is oxidized at a reaction site which is at the positive side of the membrane,... 

Cytochromes, as components of electron transfer chains, must interact with the other components, accepting electrons from reduced donor molecules and transferring them to appropriate acceptors. In the respiratory chain of the mitochondria, the ubiquinolxytochrome c oxidoreductase, QCR or cytochrome bc complex, transfers electrons coming from Complexes 1 and 11 to cytochrome c. The bc complex oxidises a membrane-localised ubiquinol the redox process is coupled to the translocation of protons across the membrane, in the so-called proton-motive Q cycle, which is presented in a simplified form in Figure 13.14. This cycle was first proposed by Peter Mitchell 30 years ago and substantially confirmed experimentally since then. The Q cycle in fact consists of two turnovers of QH2 (Figure 13.14). In both turnovers, the lipid-soluble ubiquinol (QH2) is oxidized in a two-step reoxidation in which the semiquinone CoQ is a stable intermediate, at the intermembrane face of the mitochondrial inner membrane. It transfers one electron to the Rieske iron—sulfur protein (ISP), one electron to one of the two cytochrome b haems (bi), while two protons are transferred to the intermembrane space. In both of the Q cycles, the cytochrome bi reduces cytochrome bfj while the Reiske iron—sulfur cluster reduces cytochrome c/. The cytochrome ci in turn reduces the water-soluble cytochrome c, which transfers its electrons to the terminal oxidase, cytochrome c oxidase, described above. In one of the two Q cycles, reduced cytochrome bf reduces Q to the semiquinone, which is then reduced to QH2 by the second reduced cytochrome bn- The protons required for this step are derived from the matrix side of the membrane. The overall outcome of the two CoQ cycles (10) (/ — matrix o — intermembrane space) is... 

FIGURE 13.14 The proton-motive Q cycle. Electron transfer reactions are numbered and circled. Dashed arrows designate movement of ubiquinol or ubiquinone between centres N and P and of the ISP between cytochrome b and cytochrome cl. Solid black bars indicate sites of inhibition by antimycin, UHDTB, and stigmatellin. From Hunte, Koepke, Lange, Rossmanith, Michel, 2000. Copyright 2000 with... 

B. L. Trumpower The proton motive Q cycle. Journal of Biological Chemistry 265, 1409(1990). 

The AG° for this reaction is sufficiently negative that two additional protons are translocated from the mitochondrial matrix across the inner membrane for each pair of electrons transferred this involves the proton-motive Q cycle discussed later. 

Fig. 21.9. The proton motive Q cycle for the b-Cj complex. (1) From 2 QH2, electrons go down two different paths one path is through an FeS center protein (ISP) toward cytochrome c (shown with blue arrows). Another path is backward to one of the b cytochromes, shown with dashed arrows. (2) Electrons are transferred from ISP through cytochrome Cj. Cytochrome c, which is in the intermembrane space, binds to the b-Cj complex to accept an electron. (3) Returning electrons go through another b cytochrome and are directed toward the matrix. (4) At the matrix side, electrons and 2H are accepted by Q. Q, Coenzyme Q Q , CoQ semiquinone QH2, CoQ hydroquinone.

Fig. 4. Scheme of proton translocation during electron transfer via (A) a loop mechanism (B) a proton-motive Q cycle. SHj and A represent the electron donor and acceptor, respectively. I, 2 and 3 are components of the electron-transfer system. Q represents quinone, circles represent electron carriers. 

However, some of the properties of electron carriers (such as their observed redox potentials) do not fit in such a simple loop model. This has led Mitchell [11] to propose a modified mechanism, the so-called proton-motive Q cycle (Fig. 4B). In this model quinones function in two separate reactions in the QH2/QH- and the Q/QH- couple. These couples have different midpoint redox potentials and would operate at the reducing and the oxidizing site of cytochrome b, respectively. During these reactions proton translocation is supposed to occur by diffusion of the quinones in the fully oxidized (Q) and fully reduced (QH2) forms through the hydrophobic environment between their successive reaction sites at both sides of the membrane. Recently some experimental support for such a role of quinones has been obtained. Alternative models which will not be discussed here, have been postulated by Papa [12] and Williams [13]. Currently there is no conclusive support for a specific model. 

A third, clearer explanation of the electron transfer, proton translocation cycle is given by Saratse. Each ubiquinol (QH2) molecule can donate two electrons. A hrst QH2 electron is transferred along a high-potential chain to the [2Fe-2S] center of the ISP and then to cytochrome Ci. From the cytochrome Cl site, the electron is delivered to the attached, soluble cytochrome c in the intermembrane space. A second QH2 electron is transferred to the Qi site via the cytochrome b hemes, bL and bn. This is an electrogenic step driven by the potential difference between the two b hemes. This step creates part of the proton-motive force. After two QH2 molecules are oxidized at the Qo site, two electrons have been transferred to the Qi site (where one ubiquinone (Qio) can now be reduced, requiring two protons to be translocated from the matrix space). The net effect is a translocation of two protons for each electron transferred to cytochrome c. Each explanation of the cytochrome bci Q cycle has its merits and its proponents. The reader should consult the literature for updates in this ongoing research area. 

Like the homologous Complex III in mitochondria, the cytochrome bci complex of purple bacteria carries electrons from a quinol donor (QH2) to an electron acceptor, using the energy of electron transfer to pump protons across the membrane, producing a proton-motive force. The path of electron flow through this complex is believed to be very similar to that through mitochondrial Complex III, involving a Q cycle (Fig. 19-12) in which protons are consumed on one side of the membrane and released on the other. The ultimate... 

Oxidative phosphorylation is the culmination of a series of energy transformations that are called cellular respiration or simply respiration in their entirety. First, carbon fuels are oxidized in the citric acid cycle to yield electrons with high transfer potential. Then, this electron-motive force is converted into a proton-motive force and, finally, the proton-motive force is converted into phosphoryl transfer potential. The conversion of electron-motive force into proton-motive force is carried out by three electron-driven proton pumps—NADH-Q oxidoreductase, Q-cytochrome c oxidoreductase, and... 

The proton-motive force generated by photoelectron transport In plant and bacterial photosystems Is augmented by operation of the Q cycle In c3Aochrome bf complexes associated with each of the photosystems. 

Complex II 698 Complex III 699 C3dochrome bci complex 699 Q cycle 700 Complex IV 700 C3dochrome oxidase 700 proton-motive force 703... 

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