Ubiquinone in the membrane

The most recent model of this membrane, the fluid mosaic model [13] is pictured in cartoon fashion in Fig. 2. In this model, the transduction proteins (complexes I-IV) are randomly dispersed in the membrane and redox equivalents are delivered from one complex to another via the mobile electron carriers cytochrome c and ubiquinone. It is necessary that cytochrome c be able to move relatively facilely from one complex to another. Thus the binding constants cannot be too high without making the associated OS rates too slow. Conversely, to prevent unproductive short circuits via cytochrome c from complex I directly to IV, there must exist molecular recognition which favors selective binding of cytochrome c to hcj and cytochrome oxidase (and perhaps disfavors binding to complex 1 or II). 

The role of ubiquinone (coenzyme Q, 4) in transferring reducing equivalents in the respiratory chain is discussed on p. 140. During reduction, the quinone is converted into the hydroquinone (ubiquinol). The isoprenoid side chain of ubiquinone can have various lengths. It holds the molecule in the membrane, where it is freely mobile. Similar coenzymes are also found in photosynthesis (plastoquinone see p. 132). Vitamins E and K (see p. 52) also belong to the quinone/hydroquinone systems. 

Electrons from both complex I and complex II are transferred to ubiquinone, a lipophilic compound residing in the membrane. 

Six ATPs will be synthesized if the aspartate-malate shuttle is used to transfer NADH generated through glycolysis to NADH in the mitochondrial matrix four molecules of ATP will be made if the glycerol phosphate shuttle delivers the electrons to ubiquinone in the inner mitochondrial membrane. 

In addition to NAD and flavoproteins, three other types of electron-carrying molecules function in the respiratory chain a hydrophobic quinone (ubiquinone) and two different types of iron-containing proteins (cytochromes and iron-sulfur proteins). Ubiquinone (also called coenzyme Q, or simply Q) is a lipid-soluble ben-zoquinone with a long isoprenoid side chain (Fig. 19-2). The closely related compounds plastoquinone (of plant chloroplasts) and menaquinone (of bacteria) play roles analogous to that of ubiquinone, carrying electrons in membrane-associated electron-transfer chains. Ubiquinone can accept one electron to become the semi-quinone radical ( QH) or two electrons to form ubiquinol (QH2) (Fig. 19-2) and, like flavoprotein carriers, it can act at the junction between a two-electron donor and a one-electron acceptor. Because ubiquinone is both small and hydrophobic, it is freely diffusible within the lipid bilayer of the inner mitochondrial membrane and can shuttle reducing equivalents between other, less mobile electron carriers in the membrane. And because it carries both electrons and protons, it plays a central role in coupling electron flow to proton movement. 

FIGURE 19-9 IMADH ubiquinone oxidoreductase (Complex I). Complex I catalyzes the transfer of a hydride ion from NADH to FMN, from which two electrons pass through a series of Fe-S centers to the iron-sulfur protein N-2 in the matrix arm of the complex. Electron transfer from N-2 to ubiquinone on the membrane arm forms QH2, which diffuses into the lipid bilayer. This electron transfer also drives the expulsion from the matrix of four protons per pair of electrons. The detailed mechanism that couples electron and proton transfer in Complex I is not yet known, but probably involves a Q cycle similar to that in Complex III in which QH2 participates twice per electron pair (see Fig. 19-12). Proton flux produces an electrochemical potential across the inner mitochondrial membrane (N side negative, P side positive), which conserves some of the energy released by the electron-transfer reactions. This electrochemical potential drives ATP synthesis. 

The lipid-soluble ubiquinone (Q) is present in both bacterial and mitochondrial membranes in relatively large amounts compared to other electron carriers (Table 18-2). It seems to be located at a point of convergence of the NADH, succinate, glycerol phosphate, and choline branches of the electron transport chain. Ubiquinone plays a role somewhat like that of NADH, which carries electrons between dehydrogenases in the cytoplasm and from soluble dehydrogenases in the aqueous mitochondrial matrix to flavoproteins embedded in the membrane. Ubiquinone transfers electrons plus protons between proteins within the... 

The b cytochromes and cytochrome c, fit into this scheme between reducing substrates and cytochrome c. The idea thus developed that the respiratory apparatus includes a chain of cytochromes that operate in a defined sequence. The next question was whether the cytochromes are all bound together in a giant complex, or whether they diffuse independently in the membrane. Before we address this point, we need to consider three other types of electron carriers that participate in the electron-transport chain flavo-proteins, iron-sulfur proteins, and ubiquinone. 

If the reaction centers of photosystem I and photosystem II are segregated into separate regions of the thylakoid membrane, how can electrons move from photosystem I to photosystem II Evidently the plastoquinone that is reduced in photosystem II can diffuse rapidly in the membrane, just as ubiquinone does in the mitochondrial inner membrane. Plastoquinone thus carries electrons from photosystem II to the cytochrome b6f complex. Plastocyanin acts similarly as a mobile electron carrier from the cytochrome b f complex to the reaction center of photosystem I, just as cytochrome c carries electrons from the mitochondrial cytochrome bct complex to cytochrome oxidase and as a c-type cytochrome provides electrons to the reaction centers of purple bacteria (see fig. 15.13). 

A range of redox centres have been found in the membranes from cells grown on glycerol and fumarate including menaquinone, ubiquinone, the iron-sulfur centres of fumarate reductase, cytochromes d, b and a, other iron-sulfur centres and molybdenum. Some of these centres may be assignable to specific enzymes, such as molybdenum to formate dehydrogenase. Other dehydrogenases (for NADH and lactate) are also present, and are linked to the cytochromes by menaquinone. However, there have been relatively few studies on the function of these components. 

The Qcycle can be summarized starting from Qp site as follows. Membrane-bound ubiquinol binds to the Qp site. During oxidation of ubiquinol the release of two protons to the mitochondrial intermembrane space is coupled to electron transfer. A ubiquinol molecule can donate two electrons when fully oxidized. The first electron is taken up by FeS cluster of ISP, then passed to heme c of cytochrome c, where it is subsequently transferred to soluble cytochrome c. Interestingly, the second electron is transferred to bound ubiquinone in the Qn site through heme and bn yielding a ubisemiquinone. At the Qn site this ubisemiquinone, which is usually unstable, is stabilized by... 

Accompanying electron flow in mitochondria, H+ is transported from the matrix side of the inner membrane to the lumen between the limiting membranes, i.e., within the cristae (Figs. 1-9 and 6-9). Certain electron flow components are situated in the membranes such that they can carry out this vectorial movement. Protein Complex I, which oxidizes NADH, apparently transfers four H+ s across the inner membrane per pair of electrons from NADH. Complex II, which oxidizes FADH2 and leads to the reduction of a ubiquinone whose two electrons move to Complex III, apparently causes no H+ s to move from the matrix to the lumen. Transport of four H+ s from the matrix to the lumen side most likely occurs through protein Complex III per pair of electrons traversing the electron transport chain. Complex IV (cytochrome oxidase) may also transport four H+ s (Fig. 6-9 summarizes these possibilities). We also note that two H+ s are necessary for the reduction of 02 to H20, and these protons can also be taken up on the matrix side (Fig. 6-9). 

By reaction with other lipid-soluhle antioxidants in the membrane or lipoprotein, including ubiquinone (Section 14.6), which is present in large amounts in all membranes as part of an electron transport chain, not just the mitochondrial inner membrane (Thomas et al., 1995 Crane and Navas, 1997 Thomas and Stocker, 2000 Villalba and Navas, 2000). 

The respiratory complexes diffuse laterally in the membrane with diffusion coefficients of 8 X 10 °-2 X 10 cm s [81-83]. Cytochrome c and ubiquinone have been quoted to diffuse at a velocity (10 cm s ) comparable to that of phospholipid molecules [84,85]. However, the bulky isoprenoid side chain of Q may slow down its mobility [86] in chromatophores, which may be compared with mitochondria, a mobility of 10 cm s has been estimated [87]. Overfield and... 

Studies with orientated membrane multilayers have suggested that the Fe-Fe axis of the FeS centre lies in the membrane plane [206,236]. Based on pH-dependent inhibition by a ubiquinone analogue, Harmon and Struble [237] placed the FeS centre on the C side of the membrane. However, their results would also be consistent with a location inside the membrane domain, provided that there is protonic communication with the aqueous C phase. The observed interactions between Q and the FeS cluster (above) suggest, together with the location of ubiquinone in the hydrophobic domain of the membrane (see below), that the FeS centre is buried within this domain. 

Coenzyme Q (ubiquinone) CoQ is a quinone with a long hydrocarbon tail. It exists as a pool of CoQ molecules dissolved in and diffusing through the lipid bilayer of the irmer membrane. Both the quinone (oxidized) and quinol (reduced) form of the cofactor can "flip" in the membrane, thus the quinone ring can freely cross. CoQ can pick up electrons one at a time from either Complex I or II, then diffuse through the bilayer until collision with complex III allows it to pass them singly to that complex. 

Coenzyme Q is a quinone derivative with a long tail consisting of five-carbon isoprene units. The number of isoprene units in the tail depends on the species. The most common form in mammals contains 10 isoprene units (coenzyme Q]o). For simplicity, the subscript will be omitted from this abbreviation because all varieties function in an identical manner. Quinones can exist in three oxidation states. In the fully oxidized state (Q), coenzyme Q has two keto groups (Figure 18.7). The addition of one electron and one proton results in the semiquinone form (QH )- The semiquinone can losea proton to form a semiquinone radical anion (Q ). The addition of a second electron and proton to the semiquinone generates ubiquinol (QHj). the fully reduced form of coenzyme Q, which holds its protons more tightly. Thus, for quinones, electron-transfer reactions are coupled to proton and release, a property that is key to transmembrane proton transport. Because ubiquinone is soluble in the membrane, a pool of Qand QH the Qpoo/— is thought to exist in the inner mitochonrial membrane. 

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