Ubiquinones, function structure

Ubiquinones have a long, isoprene-derived side chain (see Spedal Topic E in WileyPLUS and Section 23.3). Ten isoprene units are present in the side chain of human ubiquinones. This part of their structure is highly nonpolar, and it serves to solubilize the ubiquinones within the hydrophobic bilayer of the mitochondrial inner membrane. Solubility in the membrane environment facilitates their lateral diffusion from one component of the electron transport chain to another. In the electron transport chain, ubiquinones function by accepting two electrons and two hydrogen atoms to become a hydroquinone. The hydroquinone form carries the two electrons to the next acceptor in the chain ... 

A naturally occurring phenazine of nonbacterial origin is the methano-phenazine (MP) (10) which has been isolated from the cytoplasmic membrane of Methanosarcina (Ms.) mazei Gol archaea. The structure, synthesis, properties, and function of this natural product will be discussed in detail since it is not only the first and so far the sole phenazine derivative from archaea, but also the first one that is acting as an electron carrier in a respiratory chain - a biologic function equivalent to that of ubiquinones in mitochondria and bacteria. 

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. 

FIGURE 19-11 Cytochrome be, complex (Complex III). The complex is a dimer of identical monomers, each with 11 different subunits. (a) Structure of a monomer. The functional core is three subunits cytochrome b (green) with its two hemes (bH and foL, light red) the Rieske iron-sulfur protein (purple) with its 2Fe-2S centers (yellow) and cytochrome ci (blue) with its heme (red) (PDB ID 1BGY). (b) The dimeric functional unit. Cytochrome c, and the Rieske iron-sulfur protein project from the P surface and can interact with cytochrome c (not part of the functional complex) in the intermembrane space. The complex has two distinct binding sites for ubiquinone, QN and QP, which correspond to the sites of inhibition by two drugs that block oxidative phosphorylation. Antimycin A, which blocks electron flow from heme bH to Q, binds at QN, close to heme bH on the N (matrix) side of the membrane. Myxothiazol, which prevents electron flow from... 

QH2 to the Rieske iron-sulfur protein, binds at QP, near the 2Fe-2S center and heme bL on the P side. The dimeric structure is essential to the function of Complex III. The interface between monomers forms two pockets, each containing a QP site from one monomer and a QN site from the other. The ubiquinone intermediates move within these sheltered pockets. 

Both the presence of methyl substituents in the tocopherols and their chromanol structures increase the ability of these compounds to form relatively stable radicals.498 499 This ability is doubtless probably important also in the function of ubiquinones and plastoquinones. Ubiquinone radicals (semiquinones) are probably intermediates in mitochondrial electron transport (Chapter 18) and radicals amounting to as much as 40% of the total ubiquinone in the NADH-ubiquinone reductase of heart mito-... 

We now recognize not only that these complexes are discrete structural units but also that they are functional units. Complete X-ray crystallographic structures are available for complexes III and IV and for much of the ATP synthase complex. As is indicated in Fig. 18-5, complexes I - IV are linked by two soluble electron carriers, ubiquinone and cytochrome c. 

Oxidation of NADH begins with complex I, also termed NADH dehydrogenase or NADH ubiquinone oxidoreductase. It contains 25 polypeptide chains, flavine mononucleotide (FMN), and several iron-sulfur centers. The function of this complex is to reduce a substance called ubiquinone (UQ or CoQ), whose structure is shown in Figure 17.5. UQ is not protein bound and can move about freely. In the process of reducing UQ, the NADH is oxidized to NAD+. It is now accepted that in complex I, NADH first reduces FMN, and the resulting FMNH2 then transfers its electrons through at least three iron-sulfur centers to UQ. As the electrons pass from NADH to UQ, two to four protons are extruded from the mitochondrial matrix across the inner membrane. 

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. 

Weiss, H., and Leonard, K., 1987, Structure and function of mitochondrial ubiquinol cytochrome c reductase and NADH ubiquinone reductase, Chemica Scripta 27B 73n 81. 

Atovaguone, USP.. 3- 4-(4-Chlorophenyl)-cyclohexyl -2-hydroxy-1.4-naphthoquinone (Mepron) is a highly lipophilic, water-insoluble analogue of ubiquinone 6. an es.sen-tial componcni of the mitochondrial electron transport chain in micmorganism.s. The. structural similarity between atovaquone and ubiquinone suggests that the former may act as an antimctabolilc for the latter and thereby interfere with the function of electron transport en/ymes. 

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