Disease relevance of Coenzyme Q

• Mixtures that have been separated with supercritical carbon dioxide include resin acids with the empirical formula C20H30O2 and ubiquinones from bacterial cell wall extracts of Legionella pneumophila [1].
• The membrane protein DsbB from Escherichia coli is essential for disulfide bond formation and catalyses the oxidation of the periplasmic dithiol oxidase DsbA by ubiquinone [2].
• Proton transfer from the bulk to the bound ubiquinone Q(B) of the reaction center in chromatophores of Rhodobacter sphaeroides: retarded conveyance by neutral water [3].
• Crystals of protein from Blastochloris viridis (formerly Rhodopseudomonas viridis) were reconstituted with ubiquinone and analyzed by monochromatic and Laue diffraction, in the dark and 3 ms after illuminating the crystal with a pulsed laser (630 nm, 3 mJ/pulse, 7 ns duration) [4].
• Although humans can synthesize coenzyme Q10, the anti-P. carinii activity and low toxicity of ubiquinone analogs such as atovaquone suggest that the electron transport chain in the pathogen may differ importantly from that in the host [5].

Psychiatry related information on Coenzyme Q

• Evidence for a defect in NADH: ubiquinone oxidoreductase (complex I) in Huntington's disease [6].
• Cholesterol amounts were highly variable but mostly unchanged, whereas ubiquinone concentrations increased by 30-100% in most regions in brains affected by Alzheimer's disease [7].
• Ubiquinone pair in the Qo site central to the primary energy conversion reactions of cytochrome bc1 complex [8].
• Physical activity markedly affects muscle tissue levels of ubiquinone [9].
• The levels of serum digoxin, HMG CoA reductase activity, and dolichol were found to be decreased in OCD and la Tourette's syndrome as well as in left hemispheric dominant individuals with a corresponding increase in RBC Na(+)-K+ ATPase activity, serum ubiquinone, and magnesium levels [10].

High impact information on Coenzyme Q

• Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone [11].
• Two ubiquinone binding sites are discussed and elucidated by TTFA binding [11].
• We found that the ability of complex II to catalyse electron transport from succinate to ubiquinone is compromised in mev-1 animals [12].
• The isoprenylated benzoquinone coenzyme Q is a redox-active lipid essential for electron transport in aerobic respiration [13].
• In yeast, Ero1p-mediated oxidative folding was shown to depend on cellular flavin adenine dinucleotide (FAD) levels but not on ubiquinone or heme, and Ero1p was shown to be a FAD-binding protein [14].

Chemical compound and disease context of Coenzyme Q

• One-step purification from Escherichia coli of complex II (succinate: ubiquinone oxidoreductase) associated with succinate-reducible cytochrome b556 [15].
• Membrane-bound quinoprotein glucose dehydrogenase (GDH) in Escherichia coli donates electrons directly to ubiquinone during the oxidation of d-glucose as a substrate, and these electrons are subsequently transferred to ubiquinol oxidase in the respiratory chain [16].
• The effect of antimycin on the ubiquinone cytochrome b-c2 (Q b-c2) oxidoreductase of the photosynthetic bacterium Rhodopseudomonas sphaeroides has been studied under controlled oxidation-reduction potential (Eh) conditions by equilibrium measurements and by rapid kinetic analysis of single turnover flash.induced electron and proton translocations [17].
• Escherichia coli quinol-fumarate reductase operates with both natural quinones, ubiquinone (UQ) and menaquinone (MQ), at a single quinone binding site [18].
• The membrane-bound pyrroloquinoline quinone (PQQ)-containing quinoprotein glucose dehydrogenase (mGDH) in Escherichia coli functions by catalyzing glucose oxidation in the periplasm and by transferring electrons directly to ubiquinone (UQ) in the respiratory chain [19].

Biological context of Coenzyme Q

• A model based on the difference between the two structures is proposed to explain the observed kinetics of electron transfer from QA-QB to QAQB- and the relative binding affinities of the different ubiquinone species in the QB pocket [20].
• The plasma membrane (PM) contains redox enzymes that provide electrons for energy metabolism and recycling of antioxidants such as coenzyme Q and alpha-tocopherol [21].
• The evidence is consistent with a function for coenzyme Q in a trans-plasma membrane electron transport system which influences cell growth [22].
• In the presence of NADH and ubiquinone-1, the vesicles also generate a membrane potential (interior negative) that is similar in magnitude to that observed in the presence of D-lactate [23].
• Although mitochondrial DNA is known to encode a limited number (<20) of the polypeptide components of respiratory complexes I, III, IV, and V, genes for components of complex II [succinate dehydrogenase (ubiquinone); succinate:ubiquinone oxidoreductase, EC 1.3.5.1] are conspicuously lacking in mitochondrial genomes so far characterized [24].

Anatomical context of Coenzyme Q

• In mammals, electron-transfer flavoprotein:ubiquinone oxidoreductase (ETFQO) and electron-transfer flavoprotein (ETF) are functionally associated, and ETF accepts electrons from at least nine mitochondrial matrix flavoprotein dehydrogenases and transfers them to ubiquinone in the inner mitochondrial membrane [25].
• It is well known that ubiquinone-10 (coenzyme Q10, ubiquinone 50) acts as an electron carrier of the respiratory chain in mitochondria [26].
• A 34-kDa coenzyme Q reductase (p34) has been purified from pig-liver plasma membranes [27].
• When ubiquinone is reincorporated into extracted submitochondrial particles, the signal is again easily produced by partial reduction [28].
• We propose that this is indicative of a defect in the respiratory chain between NADH and coenzyme Q, for the first time demonstrable in cultured skin fibroblasts [29].

Associations of Coenzyme Q with other chemical compounds

• The prenylcysteine content of mammalian tissue is about 1% of that of cholesterol and about equal to that of ubiquinones and dolichols [30].
• DsbB, in turn, is oxidized by two kinds of quinones (ubiquinone for aerobic and menaquinone for anaerobic growth) in the electron-transport chain [31].
• These data suggest that in the normal protein the flavin center accepts electrons from ETF and that the 4Fe4S cluster reduces ubiquinone [32].
• Analysis of 70 different amino acid sequences of the ND6 subunit indicated that the 14484 mutation affects an amino acid belonging to its most conserved region, which shows local similarities with cytochrome b regions interacting with ubiquinone or ubiquinol in complex III [33].
• Vitamin E and selenium deficiency induces expression of the ubiquinone-dependent antioxidant system at the plasma membrane [34].

Gene context of Coenzyme Q

• Reproductive fitness and quinone content of Caenorhabditis elegans clk-1 mutants fed coenzyme Q isoforms of varying length [35].
• Complementation of Saccharomyces cerevisiae coq7 mutants by mitochondrial targeting of the Escherichia coli UbiF polypeptide: two functions of yeast Coq7 polypeptide in coenzyme Q biosynthesis [36].
• Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis [37].
• The membrane intrinsic domain, consisting of Sdh3p and Sdh4p, is proposed to bind two molecules of ubiquinone and one heme [38].
• The Saccharomyces cerevisiae succinate-ubiquinone oxidoreductase. Identification of Sdh3p amino acid residues involved in ubiquinone binding [39].

Analytical, diagnostic and therapeutic context of Coenzyme Q

• In fact, that was the length of the ubiquinone extracted from epimastigotes, as determined by high-performance liquid chromatography [40].
• Upon titration of the recombinant protein with ubiquinone, a saturation behavior is observed, suggesting that the binding is specific and that the recombinant protein may be in the functionally active state [41].
• Site-directed mutagenesis of residues in the CoQ-binding site significantly reduced inhibitor potency [42].
• Two cDNAs encoding geranyl diphosphate:4-hy- droxybenzoate 3-geranyltransferase were isolated from Lithospermum erythrorhizon by nested PCR using the conserved amino acid sequences among polyprenyl- transferases for ubiquinone biosynthesis [43].
• There was no significant difference in left ventricular ejection fraction, cardiac volumes or hemodynamic and quality of life indices after treatment with coenzyme Q or placebo, although plasma coenzyme Q levels increased from 903 +/- 345 nmol/l(-1) to 2,029 +/- 856 nmol/l(-1) [44].

References