Ubiquinol: an endogenous antioxidant in aerobic organisms

Springer Science and Business Media LLC - Tập 71 - Trang S60-S65 - 1993
L. Ernster1, P. Forsmark-Andrée1,2
1Department of Biochemistry, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
2Clinical Research Center, Huddinge Hospital, Karolinska Institute, Sweden

Tóm tắt

Ubiquinone (coenzyme Q), in addition to its function as an electron and proton carrier in mitochondrial and bacterial electron transport linked to ATP synthesis, acts in its reduced form (ubiquinol) as an antioxidant, preventing the initiation and/or propagation of lipid peroxidation in biological membranes and in serum low-density lipoprotein. The antioxidant activity of ubiquinol is independent of the effect of vitamin E, which acts as a chain-breaking antioxidant inhibiting the propagation of lipid peroxidation. In addition, ubiquinol can efficiently sustain the effect of vitamin E by regenerating the vitamin from the tocopheroxyl radical, which otherwise must rely on water-soluble agents such as ascorbate (vitamin C). Ubiquinol is the only known lipid-soluble antioxidant that animal cells can synthesize de novo, and for which there exist enzymic mechanisms that can regenerate the antioxidant from its oxidized form resulting from its inhibitory effect of lipid peroxidation. These features, together with its high degree of hydrophobicity and its widespread occurrence in biological membranes and in low-density lipoprotein, suggest an important role of ubiquinol in cellular defense against oxidative damage. Degenerative diseases and aging may bc 1 manifestations of a decreased capacity to maintain adequate ubiquinol levels.

Tài liệu tham khảo

Åberg F, Appelkvist E-L, Dallner G, Ernster L (1992) Distribution and redox state of ubiquinones in rat and human tissues. Arch Biochim Biophys 295:230–234 Ames BN (1989) Endogenous oxidative DNA damage, aging and cancer. Free Rad Res Commun 7:121–128 Appelkvist E-L, Kalén A, Dallner G (1991) Biosynthesis and regulation of coenzyme Q. In: Folkers K, Littarru GP, Yamagami T (eds) Biomedical and clinical aspects of coenzyme Q, vol 6. Elsevier, Amsterdam, pp 141–150 Asada K, Takahashi M (1987) Production and scavenging of active oxygen in photosynthesis. In: Kyle DJ, Osmond CB, Arntzen CJ (eds) Photoinhibition. Elsevier, Amsterdam, pp 227–287 Bäckström D, Norling B, Ehrenberg A, Ernster L (1970) Electron spin resonance measurement on ubiquinone-depleted and ubiquinone-replenished submitochondrial particles. Biochim Biophys Acta 197:108–111 Beyer RE (1988) Inhibition by coenzyme Q of ethanol- and carbontetrachloride-stimulated lipid peroxidation in vivo catalyzed by microsomal and mitochondrial systems. Free Rad Biol Med 5:297–303 Beyer RF, Ernster L (1990) The antioxidant role of coenzyme Q. In: Lenaz G, Barnabei O, Rabbi A, Battino M (eds) Highlights in ubiquinone research. Taylor & Francis, London, pp 191–213 Beyer RE, Noble WM, Hirschfeld TJ (1962) Coenzyme Q (ubiquinone) levels of tissues of rats during acclimation to cold. Can J Biochem 40:511–518 Beyer RE, Noble WM, Hirschfeld TJ (1962) Alterations of rat-tissue coenzyme Q (ubiquinone) levels by various treatments. Biochim Biophys Acta 57:376–379 Beyer RE, Burnett B-A, Cartwright KJ, Edington DW, Falzon MJ, Kreitman KR, Kuhn TW, Ramp BJ, Rhee SYS, Rosenwasser MJ, Stein M, An LCI (1985) Tissue coenzyme Q(ubiquinone) and protein concentrations over the life span of the laboratory rat. Mech Ageing Dev 32:267–281 Beyer RE, Nordenbrand K, Ernster L (1986) The role of coenzyme Q as a mitochondrial antioxidant: A short review. In: Folkers K, Yamamura Y, (eds) Biomedical and clinical aspects of coenzyme Q, vol 5. Elsevier, Amsterdam, pp 17–24 Beyer RE, Nordenbrand K, Ernster L (1987) The function of coenzyme Q in free radical production and as an antioxidant: a review. Chemica Scripta 27:145–153 Burton GW, Joyce A, Ingold KU (1983) Is vitamin E the only lipid-soluble chain-breaking antioxidant in human plasma and erythrocyte membranes? Arch Biochem Biophys 221:281–290 Cadenas E, Hochstein P, Ernster L (1992) Pro- and antioxidant functions of quinones and quinone reductases in mammalian cells. Adv Enzymol 65:97–146 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, vol 1. Elsevier, Amsterdam, pp 3–14 Crane FL, Sun IL, Clark MG, Grebing C, Löw H (1985) Transplasma membrane redox systems in growth and development. Biochim Biophys Acta 811:233–264 Cutler RG (1985) Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species. Proc Natl Acad Sci USA 82:4798–480 Diplock A, Machlin L, Packer L, Pryor WA (eds) (1989) Vitamin E: biochemistry and health implications. Ann NY Acad Sci vol 570 Elmberger PG, Kalén A, Brunk U, Dallner G (1989) Discharge of newly-synthesized dolichol, dolichyl phosphate and ubiquinone with lipoproteins to rat liver perfusate and to the bile. Lipids 24:919–930 Ernster L (1984) Ubiquinone: redox coenzyme, hydrogen carrier, antioxidant. In: Folkers K, Yamamura Y (eds) Biomedical and clinical aspects of coenzyme Q, vol 4. Elsevier, Amsterdam, pp 3–13 Ernster L (1993) Lipid peroxidation in biological membranes. In: Yagi K (ed) Active oxygens, lipid peroxides and antioxidants. Japan Scientific Societies Press, Tokyo (in press) Ernster L, Beyer RE (1991) Antioxidant functions of coenzyme Q: some biochemical- and pathophysiological implications. In: Folkers K, Littarru G, Yamagami T (eds) Biomedical and clinical aspects of coenzyme Q, vol 6. Elsevier, Amsterdam, pp 45–58 Ernster L, Lee CP (1990) Thirty years of mitochondrial pathophysiology: from Luft's disease to oxygen toxicity. In: Kim CH, Ozawa T (eds) Bioenergetics: molecular biology, biochemisstry and pathology. Plenum NY, pp 451–465 Ernster L, Lee IY, Norling B, Persson B (1969) Studies with ubiquinone-depleted submitochondrial particles. Essentiality of ubiquinone for the interaction of succinate dehydrogenase, NADH dehydrogenase, and cytochrome b. Eur J Biochem 9:299–310 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. BioFactors 3:241–248 Forsmark P, Åberg 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 Forsmark P, Nordenbrand K, Ernster L (1992) Ubiquinol and vitamin E as inhibitors of lipid peroxidation in biological membranes. In: Ursini F, Cadenas E (eds) Biological free radical oxidations and antioxidants. CLEUP, Padova, pp 79–85 Frei B, Kim MC, Ames BN (1990) Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci USA 87:4878–4883 Harman D (1983) The free-radical theory of ageing: consequences of mitochondrial ageing. Age 6:86–92 Heath RL, Packer L (1968) Photoperoxidation of chloroplasts. I. Kinetics and stochiometry of fatty acid peroxidation. Arch Biochem Biophys 125:189–198 Heath RL, Packer L (1968) Photoperoxidation of chloroplasts. II. Role of electron transfer. Arch Biochem Biophys 125:850–857 Hiramatsu M, Velasco RD, Wilson DS, Packer L (1991) Ubiquinone protects against loss of tocopherol in rat liver microsomes and mitochondrial membranes. Res Commun Chem Pathol Pharrnacol 72:231–241 Hundal T, Forsmark P, Ernster L, Andersson B (1992) Antioxidant activity of reduced plastoquinone in thylakoid membranes during strong illumination. EBEC Short Reports, vol 7. Elsevier, Amsterdam, p 66 Jayaraman J, Ramasarma T (1963) Intracellular distribution of coenzyme Q in rat liver. Arch Biochem Biophys 103:258–266 Kagan V, Serbinova E, Packer L (1990) Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 169:851–857 Kalén A, Norling B, Appelkvist E-L, Dallner G (1987) Ubiquinone biosynthesis by the microsomal fraction from rat liver. Biochim Biophys Acta 926:70–78 Kalén A, Appelkvist E-L, Dallner G (1989) Age-related changes in the lipid composition of rat and human tissue. Lipids 24:579–584 King TE (1985) Ubiquinone roteins. In: Lenaz G (ed) Coenzyme Q: Biochemistry, bioenergetics and clinical applications of ubiquinone. Wiley, New York, pp 391–408 Kröger A, Klingenberg M (1973) The kinetics of the redox reactions of ubiquinone related to the electron-transport activity in the respiratory chain. Eur J Biochem 34:358–368 Lea CH, Kwietny A (1962) The antioxidant properties of ubiquinone and related compounds. Chemical Industry (London) 24:1245–1246 Lind C, Cadenas E, Hochstein P. Ernster L (1990) DT-diaphorase: purification, properties, and function. Meth Enzymol 186:287–301 Linnane AW, Marzuki S, Ozawa T, Tanaka M (1988) Mitochondrial DNA mutations as an important contributor to ageing an degenerative diseases. Lancet 1:642–641 Luft R, Ikkos D, Palmieri G, Ernster L, Afzelius B (1962) A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical and morphological study. J Clin Invest 41:1776–1801 Maguire JJ, Wilson D, Packer L (1989) Mitochondrial electron transport-linked tocopheroxyl radical reduction. J Biol Chem 264:21462–21465 Mellors A, Tappel AL (1966) Quinones and quinols as inhibitors of lipid peroxidation. Lipids 1:282–284 Mellors A, Tappel AL (1966) The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol. J Biol Chem 241:4353–4356 Miller DM, Buettner GB, Aust SD (1990) Transition metals as catalysts of “autoxidation” reactions. Free Rad Biol Med 8:95–108 Mitchell P (1976) Possible molecular mechanisms of the protomnotive function of cytochrome systems. J Theor Biol 62:327–367 Mohr D, Bowry VW, Stocker R (1992) Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta 1126:247–254 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 Niki E (1987) Antioxidants in relation to lipid peroxidation. Chem Phys Lip 44:227–251 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 activities. Eur J Biochem 47:475–482 Pacifici RE, Davies KJA (1990) Protein degradation as an index of oxidative stress. Meth Enzymol 186:485–502 Pedersen S, Tata JR, Ernster L (1963) Ubiquinone (coenzyme Q) and the regulation of basal metabolic rate by thyroid Hormones. Biochim Biophys Acta 69:407–409 Quinn PJ, Katsikas H (1985) Thermal characteristics of coenzyme Q and its interaction with model membrane systems. In: Lenaz G (ed) Coenzyme Q: biochemistry, bioenergetics and clinical applications of ubiquinone. Wiley, New York, pp 107–130 Richter C (1988) Do mitochondrial DNA fragments promote cancer and aging? FEBS Lett 241:1–5 Richter C, Park J-W, Ames BN (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci USA 85:6465–6467 Sottocasa G, Kuylenstiema B, Ernster L, Bergstrand A (1967) An electron-transport system associated with the outer membrane of liver mitochondria. A biochemical and morphological study. J Cell Biol 32:415–438 Stadtman ER, Oliver CN (1991) Metal-catalyzed oxidation of proteins. Physiological consequences. J Biol Chem 266:2005–2008 Stocker R, Bowry VW, Frei B (1991) Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol. Proc Natl Acad Sci USA 88:1646–1650 Takayanagi R, Takeshige K, Minakami S (1980) NADH-and NADPH-dependent lipid peroxidation in bovine heart submitochondrial particles. Biochem J 192:853–860 Takeshige K, Minakami S (1975) Reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation by beef heart submitochondrial particles. J Biochem 77:1067–1073 Takeshige K, Takayanagi R, 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 Tappel AL (1972) Vitamin E and free radical peroxidation of lipids. Ann NY Acad Sci 203:12–21 VERIS (1992) Vitamin E research summary on the possible protective role of antioxidants in development of coronary heart disease. LaGrange IL, February Yagi K (1987) Membrane damage provoked by lipid peroxides. In: Kim CH, Tedeschi H, Diwan J-J, Salerno JC (eds) Advances in membrane biochemistry and bioenergetics. Plenum, New York, pp 553–560 Yamamoto Y, Kawamura M, Tatsuno K, Yamashita S, Niki E, Naito C (1991) Formation of lipid hydroperoxides in the cupric ion-induced oxidation of plasma and low density lipoprotein. In: Davies KJA (ed) Oxidative damage and repair: chemical, biological and medical aspects. Pergamon, London, pp 287–291 Zhang J-R, Sevanian A (1991) Effect of vitamin E on arachidonic acid peroxidation and its binding to Chinese hamster V79 cell DNA. Biochim Biophys Acta 1085:159–166