Free Radical Formation and Antioxidant Protection in Extracellular Fluids

  • John M. C. Gutteridge
Part of the NATO ASI Series book series (NSSA, volume 189)


The present. oxygen concentration of dry air is 21% (v/v) and aerobic life processes utilize molecular oxygen for the controlled oxidation of carbon-containing molecules in order to release energy and heat. Molecular oxygen is itself a radical with two unpaired electrons with parallel spins. Most incoming electrons would have opposite spins and therefore be restricted in their reactions with oxygen. This restriction considerably slows down the reaction of oxygen with non-radicals. Unfortunately, it also results in the formation of univalent reduction intermediates with unpaired electrons such as the hydroperoxyl radical (HO. 2), superoxide anion (0- 2) and the hydroxyl radical (•OH). At physiological pH values HO2 will yield the superoxide anion which is also formed in numerous metabolic processes (for reviews see Halliwell and Gutteridge 1985)1,2. Superoxide is able to do some direct damage in biological systems3 but is not considered a particularly aggressive oxidant. Nevertheless generation of 0- 2 has consistently been shown to accompany significant damage to biological molecules.4,5 The currently preferred explanation is that damage is usually mediated by a highly aggressive oxidant such as the hydroxyl radical. The chemical reaction sequence leading to •OH formation has been shown to involve hydrogen peroxide (H2O2) and a transition metal complex, with a variable oxidation number, and is known as the ‘Superoxide-driven Fenton’ reaction.


Extracellular Fluid Diene Conjugation Ferroxidase Activity Hydroperoxyl Radical Transfusional Iron Overload 


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  1. 1.
    B. Halliwell and J. M. C. Gutteridge, Free Radicals in Biology and Medicine, Oxford University Press, Oxford (1985).Google Scholar
  2. 2.
    B. Halliwell and J. M. C. Gutteridge, Mol. Aspects Med, 8; 89–193.Google Scholar
  3. 3.
    I. Fridovich, Arch. Biochem. Biophys. 247; 1–11 (1988).Google Scholar
  4. 4.
    I. Fridovich, Adv. Enzymol. 41; 35–48 (1974).PubMedGoogle Scholar
  5. 5.
    I. Fridovich, Science 209, 875–877 (1978).CrossRefGoogle Scholar
  6. 6.
    J. M. C. Gutteridge, In Oxygen Radicals and Tissue Injury, Proc. UpJohn Symposium, Michigan, pp. 9–19 (1987).Google Scholar
  7. 7.
    J. M. C. Gutteridge, FEBS Lett. 201, 291–295 (1986)PubMedCrossRefGoogle Scholar
  8. 8.
    A. Puppo and B. Halliwell, Free Rad. Res. Commun. 4, 415–422 (1988)CrossRefGoogle Scholar
  9. 9.
    J. M. C. Gutteridge, T. Westermarck and B. Halliwell, In Free Radicals, Aging and Degenerative Diseases, J. E. Johnson, Jr., R. Walford, D. Harmar and J, Miguel, eds., Alan R. Liss Inc., New York, pp. 99–139. (1985).Google Scholar
  10. 10.
    J. M. C. Gutteridge, T. Westermarck and B. Halliwell, In Free Radicals, Aging and Degenerative Diseases, J. E. Johnson, Jr., R. Walford, D. Harmar and J, Miguel, eds., Alan R. Liss Inc., New York, pp. 99–139. (1985).Google Scholar
  11. 11.
    J. M. C. Gutteridge, Biochim. Biophys. Acta., 869, 119–127, (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    O. I. Aruoma and B. Halliwell, Biochem. J. 241, 273–278 (1987).PubMedGoogle Scholar
  13. 13.
    J. M. C. Gutteridge Biochem. J. 245, 415–421 (1987).PubMedGoogle Scholar
  14. 14.
    R. G. Batey, P. L. C. Fong, S. Shamir and S. Sherlock, Dig. Dis. Sci. 25, 40–60 (1980).CrossRefGoogle Scholar
  15. 15.
    M. L Groves, J. Amer. Chem. Soc. 82, 3345–3350 (1960).CrossRefGoogle Scholar
  16. 16.
    B. C. Johansson, Acta Chem. Scanda. 14, 341–350 (1960).Google Scholar
  17. 17.
    F. W. Putnam, In the Plasma Protiens, F. W. Putnam, ed., Academic Press, New York, pp. 1–50 (1975).Google Scholar
  18. 18.
    A. Smith and W. T. Morgan, Biochem. J. 182, 47–54 (1979).PubMedGoogle Scholar
  19. 19.
    J. M. C. Gutteridge and A. Smith, Biochem. J., In Press, (1988).Google Scholar
  20. 20.
    A. Samuni, M. Chevion and G. Czapski, J. Biol. Chem. 256, 12632–12635 (1981).PubMedGoogle Scholar
  21. 21.
    M. Wasil, B. Halliwell, D. C. Hutchison and H. Baum, Biochem. J. 243, 219–227 (1987).PubMedGoogle Scholar
  22. 22.
    D. D. M. Wayner, G. W. Burton, K. U. Ingold and S. Locke, FEBS Lett. 187, 33–37 (1985).PubMedCrossRefGoogle Scholar
  23. 23.
    F. J. Carver, D. Farb and E. Frieden, Biol. Tr. Elem. Res. 4, 1–19 (1981).CrossRefGoogle Scholar
  24. 24.
    S. Osaki, D. A. Johnson and E. Frieden, J. Biol. Chem. 241, 2746–2751 (1966).PubMedGoogle Scholar
  25. 25.
    E. Frieden and S. Osaki, In Effects of metals subcellular elements and macromolecules, J. Mariloff, J. R. Coleman and M. W. Miller, eds., (C. C. Thomas, Springfield, III.) Chapter 3 (1970).Google Scholar
  26. 26.
    J. M. C. Gutteridge and J. Stocks, CRC Crit. Rev. Clin. Lab. Sci. 14, 257–329 (1981).CrossRefGoogle Scholar
  27. 27.
    J. Stocks, J. M. C. Gutteridge, R. J. Sharp and T. L. Dormandy, Clin. Sci. Mol. Med. 47, 223–233 (1974).PubMedGoogle Scholar
  28. 28.
    R. W. Topham and E. Frieden, J. Biol. Chem. 245, 6698–6705 (1970).PubMedGoogle Scholar
  29. 29.
    J. M. C. Gutteridge, P. G. Winyard, D. R. Blake, J. Lunec, S. Brailsford and B. Halliwell, Biochem. J. 230, 517–523 (1985).PubMedGoogle Scholar
  30. 30.
    I. M. Goldstein, H. B. Kaplan, H. S. Edelson and G. Weissmann, J. Biol. Chem. 254, 4040–4045 (1979).PubMedGoogle Scholar
  31. 31.
    D. R. Blake, N. D. Hall, D. A. Treby, B. Halliwell and J. M. C. Gutteridge, Clin. Sci. 61, 483–486 (1981).PubMedGoogle Scholar
  32. 32.
    J. V. Bannister, W. H. Hill, H. A. 0. H.ll, J. F. Mahood, R. L. Wilson and B. S. Wolfenden, FEBS Lett. 118, 127–129 (1980).Google Scholar
  33. 33.
    B. Halliwell and J. M. C. Gutteridge, Lancet ii, 556. (1982).Google Scholar
  34. 34.
    S. L. Markland, J. Free Rad. Biol. Med. 2, 255–260 (1986).Google Scholar
  35. 35.
    D. J. McKee and E. Frieden, Biochemistry 10, 3880–3883.Google Scholar
  36. 36.
    J. M. C. Gutteridge, C. Hill and D. R. Blake, Clin. Chim. Acta. 139, 85–90 (1984).PubMedCrossRefGoogle Scholar
  37. 37.
    L. Calabrese and M. Carboraro, Biochim. J. 238, 291–295 (1986).Google Scholar
  38. 38.
    S. L. Markland, E. Holme and L. Hellner, Clin. Chim. Acta. 126, 41–51 (1982).CrossRefGoogle Scholar
  39. 39.
    K. R. Maddipati, C. Gasparski and L. J. Marnett, Arch. Biochem. Biophys. 254, 9–17 (1987).PubMedCrossRefGoogle Scholar
  40. 40.
    K. Takahashi, N. Avissar, J. Whitin and H. Cohen, Arch. Biochem. Biophys. 256, 677–686 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • John M. C. Gutteridge
    • 1
  1. 1.Molecular Toxicology Research Group Oklahoma Medical Research Foundation 825Oklahoma CityUSA

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