Ubiquinone, electron transfer function

The redox properties of quinones are crucial to the functioning of living cells, where compounds called ubiquinones act as biochemical oxidizing agents to mediate the electron-transfer processes involved in energy production. Ubiquinones, also called coenzymes Q, are components of the cells of all aerobic organisms, from the simplest bacterium to humans. They are so named because of their ubiquitous occurrence in nature. 

Over the years, there have been numerous reports of oxidase preparations that contain polypeptide components, additional to those described above. As yet no molecular probes are available for these, and so their true association with the oxidase is unconfirmed. There are many reports in the literature describing the role of ubiquinone as an electron transfer component of the oxidase, but its involvement is controversial. Quinones (ubiquinone-10) have reportedly been detected in some neutrophil membrane preparations, but other reports have shown that neither plasma membranes, specific granules nor most oxidase preparations contain appreciable amounts of quinone, although some is found in either tertiary granules or mitochondria. Still other reports suggest that ubiquinone, flavoprotein and cytochrome b are present in active oxidase preparations. Thus, the role of ubiquinone and other quinones in oxidase activity is in doubt, but the available evidence weighs against their involvement. Indeed, the refinement of the cell-free activation system described above obviates the requirement for any other redox carriers for oxidase function. 

The first of these new, electron transferring components was coenzyme Q (CoQ). Festenstein in R.A. Morton s laboratory in Liverpool had isolated crude preparations from intestinal mucosa in 1955. Purer material was obtained the next year from rat liver by Morton. The material was lipid soluble, widely distributed, and had the properties of a quinone and so was initially called ubiquinone. Its function was unclear. At the same time Crane, Hatefi and Lester in Wisconsin were trying to identify the substances in the electron transport chain acting between NADH and cytochrome b. Using lipid extractants they isolated a new quininoid coenzyme which showed redox changes in respiration. They called it coenzyme Q (CoQ). CoQ was later shown to be identical to ubiquinone. 

Cytochrome bci is a multicomponent enzyme found in the inner mitochron-drial membrane of eukaryotes and in the plasma membrane of bacteria. The cytochrome bci complex functions as the middle component of the mitochondrial respiratory chain, coupling electron transfer between ubiquinone/ ubiquinol (see Figure 7.27) and cytochrome c. 

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. 

Complex III Ubiquinone to Cytochrome c The next respiratory complex, Complex III, also called cytochrome focx complex or ubiquinone icytochrome c oxidoreductase, couples the transfer of electrons from ubiquinol (QH2) to cytochrome c with the vectorial transport of protons from the matrix to the intermembrane space. The determination of the complete structure of this huge complex (Fig. 19-11) and of Complex IV (below) by x-ray crystallography, achieved between 1995 and 1998, were landmarks in the study of mitochondrial electron transfer, providing the structural framework to integrate the many biochemical observations on the functions of the respiratory complexes. 

All Parts of Ubiquinone Have a Function In electron transfer, only the quinone portion of ubiquinone undergoes oxidation-reduction the isoprenoid side chain remains unchanged. What is the function of this chain ... 

Step 2 Complex III. The cytochrome b-c 1 complex (Complex III) consists of at least 11 polypeptides and functions as a dimer. It accepts electrons from ubiquinone and transfers them to the next carrier, cytochrome c (CytC). This reaction pumps four protons (2 protons/electron) to the intermembrane space. 

Ubiquinones are energy transducers that are obligatory in many respiratory and photosynthetic electron transport chains. The ubiquinone enzymes involved in these reactions usually function in a manner that couples the electron transfer by the ubiquinone to proton translocation across the membrane.The structural makeup of the ubiquinone active site permits varying functional roles that influence the electron and proton chemistry. 

Despite lack of sequence homology, the function of the quinone reduction site (Qi site) is similar to that of the secondary quinone-binding site (Qb site) of bacterial reaction centers. Both sites have a conserved histidine residue as quinone ligand and both quinone molecules are reduced to hydroquinone in two consecutive one-electron transfer steps. The midpoint potential for the first step is pH-independent at near neutrality, whereas that for the second reduction varies by 120mV per pH unit (Robertson et al., 1984). This suggests a reaction pathway Q —> Q" QH2, with both protons added concomitantly with the second electron. A stable semi-quinone anion intermediate can be detected by EPR spectroscopy of samples frozen during turnover (Yu et al., 1980 de Vries et al., 1980) or with the redox potential adjusted near the midpoint of ubiquinone (Robertson et al., 1984 Ohnishi and Trumpower, 1980). The semiquinone signal is not observed in the presence of antimycin, which is consistent with the proposal that antimycin inhibits the reaction at the site (Mitchell, 1976 Mitchell, 1975). 

There is one bacterial system where such reversed electron transfer is of great importance. In Rps. sphaeroides the generated by cyclic electron flow through the reaction centre and cytochrome system is used to induce reversed electron flow from the level of the ubiquinone pool to the NADH/NAD" pool, in a manner analogous to that described for mitochondria. The role of this is to supply low potential electrons for the biosynthetic functions of the cell [38]. 

The general function of this complex is that of transferring electrons from ubiquinone (or plastoquinone) to a hydrophilic protein acceptor (cytochrome c or plastocyanin). Therefore, in bacterial photosynthesis, it catalyzes the recycling of electrons from the secondary electron acceptor (Qn) to the secondary electron donor (cyt. Cj), completing thereby the cyclic electron transfer system. In chloroplasts and cyanobacteria, an analogous system transfers the electrons from plastoquinone (the secondary acceptor of PSII, A, 3) to plastocyanin (the secondary donor to PSI, 0, 2) and provides in this way an intersystem redox connection between PSII and PSI. The same complex is also involved in the cycling of electrons around PSI. 

Whereas redox reactions on metal centres usually only involve electron transfers, many oxidation/reduction reactions in intermediary metabolism, as in the case above, involve not only electron transfer, but hydrogen transfer as well — hence the frequently used denomination dehydrogenase . Note that most of these dehydrogenase reactions are reversible. Redox reactions in biosynthetic pathways usually use NADPH as their source of electrons. In addition to NAD and NADP+, which intervene in redox reactions involving oxygen functions, other cofactors like riboflavin (in the form of flavin mononucleotide, FMN, and flavin adenine dinucleotide, FAD) (Figure 5.3) participate in the conversion of [—CH2—CH2— to —CH=CH—], as well as in electron transfer chains. In addition, a number of other redox factors are found, e.g., lipoate in a-ketoacid dehydrogenases, and ubiquinone and its derivatives, in electron transfer chains. 

We first examine briefly the binding domains of the primary (Qa) and secondary (Qb) quinone-acceptor molecules in the bacterial reaction centers, and see how one can rationalize their functional relationship. In Rp. viridis, the two quinones are different, Qa being menaquinone-7 and Qb ubiquinone-10. In this case, electron transfer from Qa to Qb could be accounted for by the difference in redox potential of the two types of quinones. In Rb. sphaeroides, however, both Qa and Qb are ubiquinone-10 and the condition for an exothermic electron transfer from Qa to Qb might be satisfied if the environments of the two quinone molecules were sufficiently different. Such differences in local structural features might also account for differences in other properties of the two quinone molecules. 

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. 

Positive feedback is obtained above electrically conductive samples. If a layer of biomolecules is placed onto a conducting sample, electron transfer at the covered areas is inhibited and the positive feedback does not reach the value recorded above the uncovered surface. In the example shown in Figure 2, a film of ubiquinone-10, deposited at the location (130 < Jt/ju,m < 220) reduces the positive feedback compared to the bare glassy carbon electrode. The biochemical function of ubiquinone as a cofactor in the respira-... 

Cytochrome b-560 has been obtained from the bacterium (Fukumori et al., 1988a), and the occurrence of two membrane-bound fr-type cytochromes has been observed (Miller and Wood, 1983). As no cytochrome is involved in the system of the oxidation of ammonia and hydroxylamine, the b-type cytochrome(s) will function in the reduction system of NAD(P)+ in which ubiquinone-8 seems to be involved (Hooper et al., 1972). Although an electron transfer pathway in which ubiquinone-8 mediates electrons between cytochrome c-554 and cytochrome c-552... 

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