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Coenzyme Q and vitamin E need each other as antioxidants

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Summary

Both vitamin E and coenzyme Q possess distinct lipoprotective antioxidant properties in biological membranes. Their combined antioxidant activity, however, is markedly synergistic when both are present together. While it is likely that vitamin E represents the initial chain-breaking antioxidant during lipid peroxidation, both fully reduced CoQH2 (ubiquinol) and semireduced CoQH. (ubisemiquinone) appear to efficiently recycle the resultant vitamin E phenoxyl radical back to its biologically active reduced form. We describe and support a potential kinetic mechanism whereby vitamin E and coenzyme Q interact in such a way as to usurp the prooxidant effects of O −.2 . Physical interactions of vitamin E and coenzyme Q within the environment of the membrane lipid bilayer facilitate the recycling of vitamin E by ubisemiquinone and ubiquinol. Lastly, data are linked into a catalytic cycle that serves to connect normal electron transport mechanisms within biological membranes to the maintenance of lipoprotective antioxidant mechanisms.

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References

  • Aranda FJ, Villalain J, Gomez-Fernandez JC (1986) A Fourier transform infrared spectroscopic study of the molecular interaction of ubiquinone-10 and ubiquinol-10 with bilayers of dipalmitoylphosphatidylcholine. Biochim Biophys Acta 861: 25–32

    CAS  Google Scholar 

  • Beyer RE (1988) Inhibition by coenzyme Q of ethanol- and carbon tetrachloride-stimulated lipid peroxidation in vivo and catalyzed by microsomal and mitochondrial systems. Free Radic Biol Med 5: 197–303

    Article  Google Scholar 

  • Booth RF, Galanopoulou DG, Quinn PJ (1982) Protection by ubiquinone and ubiquinol against lipid peroxidation in egg yolk phosphatidylcholine liposomes. Biochem Int 5: 151–156

    CAS  Google Scholar 

  • Boveris A, Cadenas E, Stoppani AOM (1976) Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochem J 156: 435–444

    PubMed  CAS  Google Scholar 

  • Bowry VW, Stocker R (1993) Tocopherol-mediated peroxidation: the prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. J Am Chem Soc 115: 6029–6044

    Article  CAS  Google Scholar 

  • Burton GW, Ingold KU (1986) Vitamin E as an in vitro and in vivo antioxidant. Ann N Y Acad Sci 570: 7–22

    Google Scholar 

  • Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15: 7–10

    Article  PubMed  CAS  Google Scholar 

  • Cipollone M, Fiorentini D, Galli MC, Sechi AM, Landi L (1994) Autooxidation and antioxidant activity of ubiquinol homologues in large unilamellar vesicles. Chem Phys Lipids 69: 87–94

    Article  PubMed  CAS  Google Scholar 

  • Cornell BA, Keniry MA, Post A, Robertson RN, Weir LE, Westerman PW (1987) Location and activity of ubiquinone-10 and ubiquinone analogs in model and biological membrane. Biochemistry 26: 7702–7707

    Article  PubMed  CAS  Google Scholar 

  • Crane FL, Morré DJ (1977) Evidence for coenzyme Q function in Golgi membranes. In: Folkers K, Yamamura Y (eds) Biomedical and clinical aspects of coenzyme Q. Elsevier, Amsterdam, pp 3–14

    Google Scholar 

  • —, Hatefi Y, Lester RL, Widmer C (1957) Isolation of a quinone from beef heart mitochondria. Biochim Biophys Acta 25: 220–221

    Article  PubMed  CAS  Google Scholar 

  • Crawford DR, Schneider DL (1983) Ubiquinone content and respiratory burst activity of latex-filled phagolysosomes isolated from neutrophils and evidence for the probable involvement of a third granule. J Biol Chem 258: 5363–5367

    PubMed  CAS  Google Scholar 

  • Ekiel IH, Hughes L, Burton GW, Joval PA, Ingold KU, Smith ICP (1988) Structure and dynamics of α-tocopherol in model membranes and in solution: a broadline and high-resolution NMR study. Biochemistry 27: 1432–1440

    Article  PubMed  CAS  Google Scholar 

  • Elmberger PG, Kalen A, Brunk UT, Dallner G (1989) Discharge of newly-synthesized dolichol and ubiquinone with lipoproteins to rat liver perfusate and to the bile. Lipids 24: 919–930

    PubMed  CAS  Google Scholar 

  • Ernster L, Forsmark P, Nordenbrand K (1992) The mode of action of lipid-soluble antioxidants in biological membranes: relationship between the effects of ubiquinol and vitamin E as inhibitors of lipid peroxidation in submitochondrial particles. J Nutr Sci Vitaminol 548: 41–46

    Google Scholar 

  • Fabisiak JP, Kagan VE, Ritov VB, Johnson DE, Lazo JS (1997) Bcl-2 inhibits selective oxidation and externalization of phosphatidylserine during paraquat-induced apoptosis. Am J Physiol Cell Physiol 272: C675-C684

    CAS  Google Scholar 

  • Forsmark P, Aberg F, Norling B, Nordenbrand K, Dallner G, Ernster L (1991) Inhibition of lipid peroxidation by ubiquinol in submitochondrial particles in the absence of vitamin E. FEBS Lett 285: 39–43

    Article  PubMed  CAS  Google Scholar 

  • Forsmark-Andree P, Dallner G, Ernster L (1995) Endogenous ubiquinol prevents protein modification accompanying lipid peroxidation in beef heart submitochondrial particles. Free Radic Biol Med 19: 749–757

    Article  PubMed  CAS  Google Scholar 

  • Frei B, Kim MC, Ames BN (1990) Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci USA 87: 4879–4883

    Article  PubMed  CAS  Google Scholar 

  • Gutman M (1980) Electron flux through the mitochondrial ubiquinone. Biochim Biophys Acta 594: 53–84

    PubMed  CAS  Google Scholar 

  • Hass MA, Massaro D (1987) Differences in CuZn superoxide dismutase induction in lungs of neonatal and adult rats. Am J Physiol 253: C66-C70

    PubMed  CAS  Google Scholar 

  • Jakobsson-Borin A, Aberg F, Dallner G (1994) Lipid peroxidation of microsomal and mitochondrial membranes extracted with n-pentane and reconstituted with ubiquinol, dolichol and cholesterol. Biochim Biophys Acta 1213: 159–166

    PubMed  CAS  Google Scholar 

  • Joenje H, Gille JJ, Oostra AB, Van der Valk P (1985) Some characteristics of hyperoxia adapted HeLa cells: a tissue culture model for cellular oxygen tolerance. Lab Invest 52: 420–428

    PubMed  CAS  Google Scholar 

  • Kagan VE (1997) Antioxidant function of NADPH-cytochrome P450 reductase: role of superoxide and coenzyme Q. In: Free radicals in liver metabolism and disease: 1st international workshop, Dinard, France, p 2

  • —, Packer L (1993) Antioxidative function of vitamin E and ubiquinols. In: Lash L, Jones D (eds) Methods in toxicology, vol 2. Academic Press, San Diego, pp 277–285

    Google Scholar 

  • —, Serbinova EA, Packer L (1990a) Recycling and antioxidant activity of tocopherol homologues of differing hydrocarbon chain length in liver microsomes. Arch Biochem Biophys 282: 221–225

    Article  PubMed  CAS  Google Scholar 

  • — — — (1990b) Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 169: 851–857

    Article  PubMed  CAS  Google Scholar 

  • — —, Safadi A, Catudioc J, Packer J (1992) NADPH-dependent inhibition of lipid peroxidation in rat liver microsomes. Biochem Biophys Res Commun 186: 74–80

    Article  PubMed  CAS  Google Scholar 

  • — —, Kahwaja S, Catudioc J, Maguire JJ, Packer L (1993) Ubiquinones and vitamin E: partners or competitors in antioxidation? In: Yagi K (ed) Active oxygens, lipid peroxides and antioxidants. CRC Press, Boca Raton, pp 237–245

    Google Scholar 

  • —, Arryoyo A, Tyurin VA, Tyurina YY, Villalba JM, Navas P (1998) Plasma membrane NADH-coenzyme Qo reductase generates semiquinone radicals and recycles vitamine E homologue in a superoxide-dependent reaction. FEBS Lett 428: 43–46

    Article  PubMed  CAS  Google Scholar 

  • Kamal-Eldin A, Appelqvist L-A (1996) The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids 31: 671–701

    Article  PubMed  CAS  Google Scholar 

  • Katsikas H, Quinn PJ (1981) The interaction of coenzyme Q with dipalmitoyl-phosphatidylcholine bilayers. FEBS Lett 133: 230–234

    Article  PubMed  CAS  Google Scholar 

  • — — (1982a) The distribution of ubiquinone-10 in phospholipid bilayers: a study using differential scanning calorimetry. Eur J Biochem 124: 165–169

    Article  PubMed  CAS  Google Scholar 

  • — — (1982b) The polyisoprenoid chain length influences the interaction of ubiquinones with phospholipid bilayers. Biochim Biophys Acta 689: 363–369

    Article  PubMed  CAS  Google Scholar 

  • Konstantinov AA, Ruuge EK (1977) Semiquinone Q in the respiratory chain of electron transport particles: electron spin resonance studies. FEBS Lett 81: 137–141

    Article  PubMed  CAS  Google Scholar 

  • Landi L, Cabrini L, Sechi AM, Pasquali P (1984) Antioxidant effect of ubiquinones on mitochondrial membranes. Biochem J 222: 463–466

    PubMed  CAS  Google Scholar 

  • — —, Tadolini B, Sechi AM, Pasquali P (1985) Incorporation of ubiquinones into lipid vesicles and inhibition of lipid peroxidation. Ital J Biochem 34: 356–363

    PubMed  CAS  Google Scholar 

  • — —, Fiorentini D, Sechi AM, Sartor G, Pasquali P, Masotti L (1990a) Coenzyme Q-3 as an antioxidant: its effect on the composition and structural properties of phospholipid vesicles. Cell Biophys 16: 1–12

    PubMed  CAS  Google Scholar 

  • —, Fiorentini D, Stefanelli C, Pasquali P, Pedulli GF (1990b) Inhibition of autooxidation of egg yolk phosphatidylcholine in homogeneous solutions and in liposomes by oxidized ubiquinone. Biochim Biophys Acta 1028: 223–228

    Article  PubMed  CAS  Google Scholar 

  • Landi L, Cabrini L, Fiorentini D, Stefanelli C, Pedulli GF (1992) The antioxidant activity of ubiquinol-3 in homogeneous solution and in liposomes. Chem Phys Lipids 61: 121–130

    Article  PubMed  CAS  Google Scholar 

  • Maguire JJ, Kagan VE, Serbinova EA, Ackrell BA, Packer L (1992) Succinate-ubiquinone reductase-linked recycling of alphatocopherol in reconstituted systems and mitochondria: requirement for reduced ubiquinone. Arch Biochem Biophys 292: 47–53

    Article  PubMed  CAS  Google Scholar 

  • Massey JB, She HS, Pownall HJ (1982) Interaction of vitamin E with saturated phospholipid vesicles and calcium. Biochem Biophys Res Commun 106: 842–847

    Article  PubMed  CAS  Google Scholar 

  • Mellors A, Tappel AL (1966a) The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol. J Biol Chem 241: 4353–4356

    PubMed  CAS  Google Scholar 

  • — — (1966b) Quinones and quinols as inhibitors of lipid peroxidation. Lipids 1: 282–284

    CAS  Google Scholar 

  • Mitchell P (1975a) Protonmotive redox mechanisms of cytochromeb-c 1 complex in the respiratory chain: protonmotive ubiquinone cycle. FEBS Lett 45: 1–6

    Article  Google Scholar 

  • — (1975b) The protonmotive Q cycle: a general formulation. FEBS Lett 59: 137–139

    Article  PubMed  CAS  Google Scholar 

  • Mukai K, Kikuchi S, Urano S (1990) Stopped-flow kinetic study of the regeneration reaction of tocopheroxyl radical by reduced ubiquinone-10 in solution. Biochim Biophys Acta 1035: 77–83

    PubMed  CAS  Google Scholar 

  • —, Morimoto H, Kikuchi S, Nagaoka S (1993) Kinetic study of free radical scavenging action of biological hydroquinones (reduced forms of ubiquinone, vitamin K and tocopherol quinone) in solution. Biochim Biophys Acta 1157: 313–317

    PubMed  CAS  Google Scholar 

  • Naumov W, Khrapova NG (1987) Chemiluminescence study of ubiquinone and ubiquinol interaction with peroxide radicals. Biophys USSR 27: 730–735

    Google Scholar 

  • Neta P, Steenken S (1982) On electron redox potentials of phenols, hydroxy and aminophenols and related compounds of biological interest. J Phys Chem 93: 7654–7659

    Article  Google Scholar 

  • Niki E, Tsuchiya J, Tanimura R, Kamiya Y (1982) The regeneration of vitamin E from alpha-chromanoxyl radical by glutathione and vitamin C. Chem Lett 6: 789–738

    Article  Google Scholar 

  • —, Kawakami A, Saito M, Yamamoto Y, Tsuchiya Y, Kamiya Y (1985) Effect of phytol side-chain of vitamin E on its antioxidant activity. J Biol Chem 260: 2191–2196

    PubMed  CAS  Google Scholar 

  • Nohl H, Jordan W, Youngman RJ (1986) Quinones in biology: functions in electron transfer and oxygen activation. Adv Free Radic Biol Med 2: 211–279

    CAS  Google Scholar 

  • Norling B, Glazek E, Nelson BD, Ernster L (1974) Studies with ubiquinone-depleted submitochondrial particles: quantitative incorporation of small amounts of ubiquinone and its effects on the NADH and succinate oxidase activites. Eur J Biochem 47: 475–482

    Article  PubMed  CAS  Google Scholar 

  • Onadorra M, Quinn PJ (1986) Proton magnetic resonance spectroscopic studies of the interaction of ubiquinone-10 with phospholipid model membranes. Eur J Biochem 155: 353–361

    Article  Google Scholar 

  • Packer JE, Slater TF, Willson RL (1979) Direct observation of a free radical interaction between E and vitamin C. Nature 278: 737–738

    Article  PubMed  CAS  Google Scholar 

  • Perly B, Smith ICP, Hughes L, Burton GW, Ingold KU (1985) Estimation of the location of natural α-tocopherol in lipid bilayers by13C-NMR spectroscopy. Biochim Biophys Acta 819: 131–135

    Article  PubMed  CAS  Google Scholar 

  • Salgado J, Villalain J, Gomez-Fernandez JC (1993) Magic-angle spinning13C-NMR spin-lattice relaxation study of the location and the effects of α-tocopherol, ubiquionone-10, ubiquionol-10 in unsonicated model membranes. Eur Biophys J 22: 151–155

    Article  CAS  Google Scholar 

  • Scarpa MA, Rigo M, Maiorino M, Ursini F, Gregolin C (1984) Formation of α-tocopherol radical and recycling of α-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. Biochim Biophys Acta 801: 215–219

    PubMed  CAS  Google Scholar 

  • Semin BK, Bautina AL, Ivanov I (1989) Thermal properties of ubiquinones. Biol Nauk 5: 32–36

    Google Scholar 

  • Spitz DR, Dewey WC, Li GC (1987) Hydrogen peroxide or heat shock induces resistance to hydrogen peroxide in Chinese hamster fibroblasts. J Cell Physiol 131: 364–373

    Article  PubMed  CAS  Google Scholar 

  • Srivastava S, Phadke RS, Govil G, Rao CNR (1983) Fluidity, permeability and antioxidant behaviour of model membranes incorporated with α-tocopherol and vitamin E acetate. Biochim Biophys Acta 734: 353–362

    Article  CAS  Google Scholar 

  • Stidham MA, MacIntosh TJ, Seidow JN (1984) On the localization of ubiquinone in phosphatidylcholine bilayers. Biochim Biophys Acta 767: 423–431

    Article  PubMed  CAS  Google Scholar 

  • Stoyanovsky DA, Goldman R, Organisciak DT, Darrow RM, Kagan VE (1995a) Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with dihydrolipoic acid. Curr Eye Res 14: 181–189

    PubMed  CAS  Google Scholar 

  • —, Osipov AN, Quinn PJ, Kagan VE (1995b) Ubiquinone-dependent recycling of vitamin E radicals by superoxide. Arch Biochem Biophys 323: 343–351

    Article  PubMed  CAS  Google Scholar 

  • Sugioka K, Nakano M, Totsune-Nakano H, Minakami H, TeroKubota S, Ikegami Y (1988) Mechanism of O −.2 generation in reduction and oxidation cycle of ubiquinones in a model of mitochondrial electron transport systems. Biochim Biophys Acta 936: 377–385

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Mayumi T, Kishi T (1988) Influence of coenzyme Q10 on doxorubicin uptake and metabolism by mouse myocardial cells in culture. Chem Pharm Bull 36: 1514–1518

    PubMed  CAS  Google Scholar 

  • Takeshige K, Takayanagi K, Minakami S (1980) Reduced coenzyme Q10 as an antioxidant of lipid peroxidation in bovine heart mitochondria. In: Yamamura Y, Folkers K, Ito Y (eds) Biomedical and clinical aspects of coenzyme Q, vol 2. Elsevier, Amsterdam, pp 15–26

    Google Scholar 

  • Turrens JF, Alexandre A, Lehninger AL (1985) Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch Biochem Biophys 237: 408–414

    Article  PubMed  CAS  Google Scholar 

  • Ulrich EL, Girving ME, Cramer WA, Markley JL (1985) Location and mobility of ubiquinones of different chain lengths in artificial membrane vesicles. Biochemistry 24: 2501–2508

    Article  PubMed  CAS  Google Scholar 

  • Urano S, Matsuo M, Sakanaka T, Uemura I, Koyama M, Kumadaki I, Fukuzawa K (1993) Mobility and molecular orientation of vitamin E in liposomal membranes as determined by19F-NMR and fluorescence. Arch Biochem Biophys 303: 10–14

    Article  PubMed  CAS  Google Scholar 

  • Wassall SR, Thewalt JL, Wong L, Gorrisen H, Cushley RJ (1986) Deuterium NMR-study of the interaction of α-tocopherol with a phospholipid model membrane. Biochemistry 25: 319–326

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto Y, Komuro E, Niki E (1990) Antioxidant activity of ubiquinol in solution and phosphatidylcholine liposome. J Nutr Sci Vitaminol 36: 505–511

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Environmental and Occupational Health, University of Pittsburgh School of Public Health, 260 Kappa Drive, RIDC Park, 15238, Pittsburgh, PA, USA

    V. E. Kagan, J. P. Fabisiak & P. J. Quinn

  2. Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania

    V. E. Kagan & J. P. Fabisiak

  3. Department of Biochemistry, King’s College London, London

    P. J. Quinn

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  1. V. E. Kagan
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  2. J. P. Fabisiak
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  3. P. J. Quinn
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Kagan, V.E., Fabisiak, J.P. & Quinn, P.J. Coenzyme Q and vitamin E need each other as antioxidants. Protoplasma 214, 11–18 (2000). https://doi.org/10.1007/BF02524257

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