Disease relevance of ubiquinol

• Projection structure of the cytochrome bo ubiquinol oxidase from Escherichia coli at 6 A resolution [1].
• Cytochrome a1 of acetobacter aceti is a cytochrome ba functioning as ubiquinol oxidase [2].
• Isolation of ubiquinol oxidase from Paracoccus denitrificans and resolution into cytochrome bc1 and cytochrome c-aa3 complexes [3].
• Discrete catalytic sites for quinone in the ubiquinol-cytochrome c2 oxidoreductase of Rhodopseudomonas capsulata. Evidence from a mutant defective in ubiquinol oxidation [4].
• Vitreoscilla hemoglobin binds to subunit I of cytochrome bo ubiquinol oxidases [5].

Psychiatry related information on ubiquinol

• Though a variety of defense mechanisms encompassing antioxidant enzymes (SOD, catalase, and GSH peroxidase and reductase), vitamins (E, C, and carotenoids), and biomolecules (GSH and ubiquinol) are available, a balance of the benefits and risks from ROS and antioxidants appears to be necessary for the survival and functioning of spermatozoa [6].
• Neurodegenerative disorders, cancer, cardiovascular diseases and diabetes mellitus and especially aging and Alzheimer's disease exhibit altered levels of ubiquinone or ubiquinol, indicating their likely crucial role in the pathogenesis and cellular mechanisms of these ailments [7].

High impact information on ubiquinol

• Complex III (CIII; ubiquinol cytochrome c reductase of the mitochondrial respiratory chain) catalyzes electron transfer from succinate and nicotinamide adenine dinucleotide-linked dehydrogenases to cytochrome c. CIII is made up of 11 subunits, of which all but one (cytochrome b) are encoded by nuclear DNA [8].
• As neither location will allow both reactions to proceed at a suitable rate, the reaction mechanism must involve movement of the extrinsic domain of the Fe-S component in order to shuttle electrons from ubiquinol to cytochrome c1 [9].
• Cytochrome bc1 transfers electrons from ubiquinol to cytochrome c and uses the energy thus released to form an electrochemical gradient across the inner membrane [9].
• Using the ultra-fast microfluidic mixer and the freeze-quenching device, coupled with EPR, we have been able to determine the presteady-state kinetics of ISP and cytochrome b(L) reduction by ubiquinol [10].
• In both cases, when ETF-QO is reduced to a two-electron reduced state (one electron at each redox center), the enzyme is primed to reduce UQ to ubiquinol via FAD [11].

Chemical compound and disease context of ubiquinol

• The structure of the ubiquinol oxidase from Escherichia coli and its ubiquinone binding site [12].
• The cytochrome bo3 ubiquinol oxidase from Escherichia coli resides in the bacterial cytoplasmic membrane and catalyzes the two-electron oxidation of ubiquinol-8 and four-electron reduction of O2 to water [13].
• Infrared and EPR studies on cyanide binding to the heme-copper binuclear center of cytochrome bo-type ubiquinol oxidase from Escherichia coli. Release of a CuB-cyano complex in the partially reduced state [14].
• Lipophilic antioxidants, like ubiquinol 9 and vitamin E, were not decreased during ischemia-reperfusion using regular buffer; however, if oxidative stress was induced by addition of H2O2 to the buffer solution during reperfusion after 20 min of ischemia, decreases in both the hydrophilic and hydrophobic antioxidants were noticeable [15].
• Nitric oxide (*NO) is able to oxidize cyclic compounds like ubiquinol; moreover, recent lines of evidence proposed a direct role of *NO and its by-product peroxynitrite in the pathophysiology of Parkinson's disease [16].

Biological context of ubiquinol

• Cell respiration is catalyzed by the heme-copper oxidase superfamily of enzymes, which comprises cytochrome c and ubiquinol oxidases [12].
• Ethane exhalation and vitamin E/ubiquinol status as markers of lipid peroxidation in ferrocene iron-loaded rats [17].
• The sequence of the cyo operon indicates substantial structural similarities between the cytochrome o ubiquinol oxidase of Escherichia coli and the aa3-type family of cytochrome c oxidases [18].
• To extend previous studies, we carried out alanine-scanning mutagenesis for selected 16-amino acid residues in subunit IV to explore subunit-subunit interactions in bo-type ubiquinol oxidase [19].
• We report here nine novel cytochrome b structures conferring a variety of respiratory sufficient phenotypes, obtained from five respiratory deficient mutations affecting a short region of the protein (positions 131-138 of the polypeptide chain), presumably belonging to the ubiquinol oxidizing center of the bc1 complex [20].

Anatomical context of ubiquinol

• Cytochrome o, one of the two terminal ubiquinol oxidases of Escherichia coli, is structurally and functionally related to cytochrome c oxidase of mitochondria and some bacteria [21].
• The purified oxidase contains four polypeptides (MrS 66,000, 35,000, 22,000, and 17,000), two b-type cytochromes (b558 and b563), and 16-17 nmol of heme b per mg of protein, and it catalyzes the oxidation of ubiquinol and other electron donors with specific activities 20- to 30-fold higher than crude membranes [22].
• An enzyme complex with ubiquinol-cytochrome c oxidoreductase, cytochrome c oxidase, and ubiquinol oxidase activities was purified from a detergent extract of the plasma membrane of aerobically grown Paracoccus denitrificans [3].
• Preincubation of submitochondrial particles with specific antibody against subunit VII prior to addition of either succinate, NADH, or the reduced form of the decyl analogue of ubiquinol resulted in an approximately 40% increase in the extent of cytochrome c1 reduction compared with controls containing preimmune serum [23].
• These properties suggest that the structural requirements for electron transfer from ubiquinol to cytochrome c are met by a small number of peptides and that the "extra" peptides occurring in the mitochondrial bc1 complexes serve some other function(s), possibly in biogenesis or insertion of the complex into that organelle [24].

Associations of ubiquinol with other chemical compounds

• Autoxidation of lipids and antioxidation by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids: unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein [25].
• Our data together with previous work on the antioxidant function of ubiquinol reported in the literature strongly suggest that ubiquinol-10 is an important physiological lipid-soluble antioxidant [26].
• When the purified glucose dehydrogenase and cytochrome o ubiquinol oxidase were reconstituted together with ubiquinone into liposomes, a membrane potential could be generated by the electron transfer at the site of the ubiquinol oxidase but not of the dehydrogenase [27].
• This enzyme has a high affinity quinone binding site (Q(H)), and the quinone bound to this site acts as a cofactor, necessary for rapid electron transfer from substrate ubiquinol, which binds at a separate site (Q(L)), to heme b [28].
• Structure analysis of the cytochrome bc1 complex in the presence and absence of Qp quinol analog inhibitors implied that a large amplitude motion of the Rieske iron-sulfur protein (ISP) is required to mediate electron transfer from ubiquinol to cytochrome c1 [29].

Gene context of ubiquinol

• In Saccharomyces cerevisiae transcription of QCR8, encoding subunit VIII of the mitochondrial ubiquinol cytochrome c oxidoreductase, is subject to glucose repression, whereas in the distantly related yeast Kluyveromyces lactis it is not [30].
• It encodes a 6.6-kD homolog of mitochondrial ubiquinol cytochrome c oxidoreductase (QCR9), subunit 9 of the bc(1) complex in yeast [31].
• A mitochondrial cytochrome b mutation but no mutations of nuclearly encoded subunits in ubiquinol cytochrome c reductase (complex III) deficiency [32].
• The purpose of this study is to evaluate the significance of the ubiquinol cytochrome c reductase UQCRFS1 gene amplification in primary breast cancers [33].
• Our results suggest that both 14484 and 14459 mutations may affect amino acids forming the interaction site of ubiquinol product, and the 14484 mutation produces a biochemical defect resembling in part that already reported for the common 11778/ND4 LHON mutation [34].

Analytical, diagnostic and therapeutic context of ubiquinol

• To elucidate the similarities as well as differences between ubiquinol and cytochrome c oxidases, we have analysed two-dimensional crystals of cytochrome bo by cryo-electron microscopy [1].
• The heme axial ligands of bd-type ubiquinol oxidase of Escherichia coli were studied by EPR and optical spectroscopies using nitric oxide (NO) as a monitoring probe [35].
• Determination of the ligands of the low spin heme of the cytochrome o ubiquinol oxidase complex using site-directed mutagenesis [36].
• The mitochondrial bc(1) complex catalyzes the oxidation of ubiquinol and the reduction of cytochrome (cyt) c. The cyt b mutation A144F has been introduced in yeast by the biolistic method [37].
• SDS-PAGE analysis revealed a differential effect on individual protein components and its prevention by ubiquinol [38].

References