Ubiquinones in the Respiratory Chain

The participation of lipophylic quionones, possessing an isoprenoid side chain of different length, is a distinctive feature of electron transport both for animals and the plant kingdom. Plastoquinones are to be found in the membranes of chloroplasts,27,28 while mitochondria contain ubiquinones.29-31 

It is well known that the extraction of the coenzyme Q by isooctane abolishes the activity of the electron transport chain. On the contrary introduction of the coenzyme Q into lipid bilayers makes it possible to model the electron transport through biomembranes.32-36 

There exist several hypotheses as to how the ubiquinone functions in the membrane. The most common one is that coenzyme Q floats freely in the membrane37 or forms a mobile Q pool27 or Q cycle38,39 Ubiquinones differ in the length of the side isoprenoid chain, consisting usually of 6-10 carbon atoms. 

It should be noted that, apparently, only the complex of coenzyme Q with protein is a really functioning system in native coupling membranes. Although an equilibrium does exist between the free and the bound coenzyme Q, nevertheless the rate of redox transformations of free Q is considerably less than that of other redox systems in the electron transport chain. Possibly, the protein in the Q-protein complex stabilizes the radical Q6H , as a result of which the latter can readily take part in the electron-exchange reaction.31 

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This complex consists of four subunits, all of which are encoded on nuclear DNA, synthesized on cytosolic ribosomes, and transported into mitochondria. The succinate dehydrogenase (SDH) component of the complex oxidizes succinate to fumarate with transfer of electrons via its prosthetic group, FAD, to ubiquinone. It is unique in that it participates both in the respiratory chain and in the tricarboxylic acid (TC A) cycle. Defects of complex II are rare and only about 10 cases have been reported to date. Clinical syndromes include myopathy, but the major presenting features are often encephalopathy, with seizures and psychomotor retardation. Succinate oxidation is severely impaired (Figure 11). 

Figure 12-8. Principles of the chemiosmotic theory of oxidative phosphorylation. The main proton circuit is created by the coupling of oxidation in the respiratory chain to proton translocation from the inside to the outside of the membrane, driven by the respiratory chain complexes I, III, and IV, each of which acts as a protonpump. Q, ubiquinone C, cytochrome c F Fq, protein subunits which utilize energy from the proton gradient to promote phosphorylation. Uncoupling agents such as dinitrophenol allow leakage of H" across the membrane, thus collapsing the electrochemical proton gradient. Oligomycin specifically blocks conduction of H" through Fq.

Mitchell, P. (1975) Protonmotive redox mechanism of the cytochrome b-c1 complex in the respiratory chain protonmotive ubiquinone cycle, FEBS Lett., 56, 1-6. 

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. 

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. 

L-selegiline alters the redox state of ubiquinone, suggesting that the flow of electrons is impaired in the respiratory chain. Furthermore, a decrease in ubiquinone levels has been observed, whereas ubiquinol (reduced ubiquinone) concentrations are increased in the striatum. Ubiquinol levels have been shown to augment as a result of impaired mitochondrial respiration. For example, ubiquinol concentrations were demonstrated to increase in tubular kidney cells exposed to complex IV inhibitors and in disease states with defects in respiratory chain components. These results are also consistent with the hypothesis that L-selegiline enhances 02 formation by altering the rate of electron transfer within the respiratory chain leading to increases in SOD activities in the mouse striatum. 

Degree of Reduction of Electron Carriers in the Respiratory Chain The degree of reduction of each carrier in the respiratory chain is determined by conditions in the mitochondrion. For example, when NADH and 02 are abundant, the steady-state degree of reduction of the carriers decreases as electrons pass from the substrate to 02. When electron transfer is blocked, the carriers before the block become more reduced and those beyond the block become more oxidized (see Fig. 19-6). For each of the conditions below, predict the state of oxidation of ubiquinone and cytochromes b, clt c, and a + a3. 

Ubiquinone. An electron carrier in the respiratory chain, ubiquinone is a small hydrophobic molecule that can move freely in inner membrane. It is also known as coenzyme Q. 

In both systems, membrane-bound ubiquinone plays crucial roles in the respiratory chain. Indeed, various quinones, including ubiquinone and menaquinone, are used to connect the redox reactions of various membrane proteins. In spite of the large amount of biochemical and biophysical data on quinone and quinone binding proteins, little structural... 

Brandt U (1999) Proton translocation in the respiratory chain involving ubiquinone - a hypothetical semiquinone switch mechanism for complex I. Biofactors 9,95-101. 

The first complex in the respiratory chain, NADH ubiquin-one oxidoreductase (complex 1), transfers two electrons from matrix NADH to ubiquinone to form ubiquinol. This... 

Famesyl pyrophosphate is used for the synthesis of ubiquinone, dolichol, and squaJenc, Ubiquinone is a cofactor in the respiratory chain of the mitochondrion, Dolichol phosphate serves as a biochemical "handle," and is used to hold the cote oligosaccharide, and to facilitate its transfer to newly made proteins in the endoplasmic reticulum, to form glycoproteins. Squalene is the product of condensation of two FFF molecules. 

The answer is b. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) The entry point into the electron transport chain for electrons from FADH2 flavoproteins is ubiquinone, which is referred to as Q or QH2 in the reduced state. Ubiquinone carries these electrons to cytochrome oxidase, the next step in the respiratory chain. This... 

CuA-/CuB-enzymes are the terminal enzymes in the respiratory chains of a multitude of organisms. In the last step of aerobic respiratory chains, cytochrome oxidases reduce oxygen to water. Dinitrogenoxide reductase reduces N20 to N2 in the last step of denitrification. The cytochrome oxidases may be subdivided into cytochrome c oxidases [274] and ubiquinone oxidases [275-278]. Whereas all cytochrome oxidases possess CuB-centers, CuA-centers only occur in cytochrome c oxidases [279], In contrast, all known dinitrogen oxide reductases possess CuA- [278,280] but no CuB-centers. 

Coenzyme Q (CoQ), also called ubiquinone, is the only electron carrier in the respiratory chain that is not a protein-bound prosthetic group. It is a carrier of hydrogen atoms, that is, protons plus electrons. The oxidized qulnone form of CoQ can accept a single electron to form a semlqulnone, a charged free radical denoted by CoQ -. Addition of a second electron... 

Cytochrome bis a dimeric membrane protein of the inner mitochondrial membrane, 000, with one heme group per subunit. In the respiratory chain it transfers electrons from ubiquinone to C. c. Also known are a C. bj from yeast, a C. bs from mitochondria, a C. bg from chloroplasts, and a C. b, as well as a C. bj62 from E. coli. 

Rotenone (4.61) an insecticide of vegetable origin, blocks the dehydrogenation of NADH in the respiratory chain, at a dilution of 10 M, by displacing ubiquinone from NADH dehydrogenase (Gutman et al., 1971). It thus prevents the oxidation of pyruvate and glutamate (but not succinate). Fish, but... 

Ubiquinone (Q) Is esentlal for the synthesis of ATP In the respiratory chain (Chapter 11)... 

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