Ubiquinol

Electrons from NADH, together with two protons, are transferred to ubiquinone to form ubiquinol by complex I (NADH ubiquinone oxidoreductase). Complex I... 

Figure 7. Mechanism of the proton-translocating ubiquinol cytochrome c reductase (complex III) Q cycle. There is a potential difference of up to 150 mV across the hydrophobic core of this complex (potential barrier represented by the vertical broken line). Cytochromes hour and b N are heme groups on the same peptide subunits of complex III which can transfer electrons across the hydrophobic core. The movement of two electrons provides the driving force to transfer two protons from the matrix to the cytosol. Diffusion of UQ and UQHj, which are uncharged, in the hydrophobic core, and lipid bilayer of the inner membrane is not influenced by the membrane potential (see Nicholls and Ferguson, 1992).

Sometimes it is stated that the extrusion of two protons from the matrix is associated with the oxidation of one molecule of ubiquinol by complex III and four with the oxidation of two molecules of reduced cytochrome c by complex IV (Hinkle et al., 1991). For the oxidation of ubiquinol by complex III in isolation (ubiquinolxytochrome c reductase) the reaction is thought to be... 

Although only two protons are pumped out of the matrix, two others from the matrix are consumed in the formation of H2O. There is therefore a net translocation of four positive charges out of the matrix which is equivalent to the extrusion of four protons. If four protons are required by the chemiosmotic mechanism to convert cytosolic ADP + Pj to ATP, then 0.5 mol ATP is made for the oxidation of one mol of ubiquinol and one mol ATP for the oxidation of 2 mols of reduced cytochrome c. These stoichiometries were obtained experimentally when ubiquinol was oxidized when complexes I, II, and IV were inhibited by rotenone, malonate, and cyanide, respectively, and when reduced cytochrome c was oxidized with complex III inhibited by antimycin (Hinkle et al., 1991). (In these experiments, of course, no protons were liberated in the matrix by substrate oxidation.) However, in the scheme illustrated in Figure 6, with the flow of two electrons through the complete electron transport chain from substrate to oxygen, it also appears valid to say that four protons are extmded by complex I, four by complex III, and two by complex 1. 

Ubiquinone, known also as coenzyme Q, plays a crucial role as a respiratory chain electron carrier transport in inner mitochondrial membranes. It exerts this function through its reversible reduction to semiquinone or to fully hydrogenated ubiquinol, accepting two protons and two electrons. Because it is a small lipophilic molecule, it is freely diffusable within the inner mitochondrial membrane. Ubiquinones also act as important lipophilic endogenous antioxidants and have other functions of great importance for cellular metabolism. ... 

In summary, in our view the principal fectors that contribute to the oxidizability of LDL assessed by the addition of a transition metal such as copper ate (1) the lipid hydroperoxide content of the LDL particle and (2) the a-tocopherol content. Other chain-breaking antioxidants such as ubiquinol and the carotenoids are present only at low concentrations in most individuals, and are unlikely to make a significant contribution. 

Ubiquinol-10 (or coenzyme Qio see Corongiu et oL, 1993) (0.4-1.0/iM range of concentrations in human plasma) has recently been proposed as a chain-breaking antioxidant (Beyer, 1990) in LDLs as the first line of defence (Stocker et oL, 1991) and in liposomal systems. 

The lag-phase measurement at 234 nm of the development of conjugated dienes on copper-stimulated LDL oxidation is used to define the oxidation resistance of different LDL samples (Esterbauer et al., 1992). During the lag phase, the antioxidants in LDL (vitamin E, carotenoids, ubiquinol-10) are consumed in a distinct sequence with a-tocopherol as the first followed by 7-tocopherol, thereafter the carotenoids cryptoxanthin, lycopene and finally /3-carotene. a-Tocopherol is the most prominent antioxidant of LDL (6.4 1.8 mol/mol LDL), whereas the concentration of the others 7-tocopherol, /3-carotene, lycopene, cryptoxanthin, zea-xanthin, lutein and phytofluene is only 1/10 to 1/300 of a-tocopherol. Since the tocopherols reside in the outer layer of the LDL molecule, protecting the monolayer of phospholipids and the carotenoids are in the inner core protecting the cholesterylesters, and the progression of oxidation is likely to occur from the aqueous interface inwards, it seems reasonable to assign to a-tocopherol the rank of the front-line antioxidant. In vivo, the LDL will also interact with the plasma water-soluble antioxidants in the circulation, not in the artery wall, as mentioned above. 

Stocker, R., Bowry, V.W. and Frei, B. (1991). Ubiquinol-10 protects human low density lipoprotein more efficiently gainst lipid peroxidation than does a-tocopherol. Proc. Natl Acad. Sci. USA 88, 1646-1650. 

Abramson J, Riistama S, Larsson G, Jasaitis A, Svensson-Ek M, Laakkonen L, Puustinen A, Iwata S. 2000. The structure of the ubiquinol oxidase from Escherichia coli and its ubiquinone binding site. Nat Struct Biol 7 910. 

Plat J and Mensink RP. 2001. Effects of diets enriched with two different plant stand ester mixtures on plasma ubiquinol-10 and fat-soluble antioxidant concentrations. Metab Clin Exp 50(5) 520-529. 

Similar to peroxynitrite, ONOOCOO- reacts with many biomolecules such as uric acid [110], oxyhemoglobin [133], melatonin [135], NADH, ubiquinol Q0, and glutathione [141], Reactions of ONOOCOO with substrates in mitochondrial matrix is accompanied by protein nitration [141]. The reaction of ONOOCOO- with GSH was so rapid that glutathione inhibited tyrosine nitration by peroxynitrite in the presence of C02 [142], The formation of ONOOCOO- increased the formation of 3-nitrotyrosine and decreased the formation of 3-hydroxytyrosine probably due to the enhanced selectivity of C03 - compared to hydroxyl radicals [143],... 

Gardner et al. [165] have shown that the redox-cycling agent phenazine methosulfate (PMS), mitochondrial ubiquinol-cytochrome c oxidoreductase, or hypoxia inactivated aco-nitase in mammalian cells. It has been proposed that the inactivation of aconitase is mediated by superoxide produced by prooxidants because the overproduction of mitochondrial MnSOD protected aconitase from inactivation by the prooxidants mentioned above except hyperoxia. Later on, the reaction of superoxide with aconitases began to be considered as one of the most important ways to NTBI generation in vivo. 

Figure 13.12 The protonmotive 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 c,. Solid black bars indicate sites of inhibition by antimycin, UHDTB and stigmatellin. (From Hunte et al., 2003. Copyright 2003, with permission from Elsevier.)...

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. 

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