The Human Serum Paraoxonase Polymorphism and Atherosclerosis

  • Michael I. Mackness
Part of the NATO ASI Series book series (NSSA, volume 266)


Human serum paraoxonase is associated with HDL and has a polymorphic distribution in Europid populations with 2 allozymes present, one with low activity and one with high activity. Paraoxonase prevents lipid peroxide generation during the Cu2+ catalysed oxidation of LDL in vitro and may therefore contribute to the in vivo protection by HDL against the development of atherosclerosis. The presence of different allozymes of paraoxonase in the population may contribute to this process if they have different efficiencies in preventing LDL oxidation.


Paraoxonase Activity Tangier Disease Lipid Peroxide Formation Serum Paraoxonase Lipid Peroxide Generation 
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  1. 1.
    Chemnitius J-M., Losch H., Losch K. and Zech R. Organophosphate detoxicating hydrolases in different vertebrate species. Comp. Biochem Physiol. 76C, 1983; 85–93.Google Scholar
  2. 2.
    Brealey C.J., Walker C.H. and Baldwin B.C. A-esterase activities in relation to the differantial toxicity of pirimiphos-methyl to birds and mammals. Pestic. Sci. 11, 1980; 546–554.CrossRefGoogle Scholar
  3. 3.
    Geldmacher-von Mallinckrodt M. and Diepgen T.L. The Human Serum Paraoxonase-Polymorphism and Specificity.Toxicol. Environm. Chem. 18, 1988; 79–196.Google Scholar
  4. 4.
    La Du B.N. and Eckerson H.W. The polymorphic paraoxonasearylestease isoenzymes of human serum. Federation Proc. 43, 1984; 2338–2341.Google Scholar
  5. 5.
    Humbert R., Adler D.A., Disteche C.M., Hassett C., Omiecinski C.J. and. Furlong C. E. The molecular basis of the human serum paraoxonase activity polymorphism. Nature genetics 3, 1993; 73–76.Google Scholar
  6. 6.
    Adkins S., Gan K.N., Mody M. and La Du B.N. Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase. Am. J. Hum Genet 52, 1993; 598–608.Google Scholar
  7. 7.
    Blatter M-C., Abbott C.A., Messmer S., Pometta D., Durrington P.N., Mackness M.I. and James R.W. In preparation.Google Scholar
  8. 8.
    Diepgen T.L. and Geldmacher-von Mallinckrodt M. Interethnic differences in the detoxification of organophosphates: The human serum paraoxonase polymorphism. Arch. Toxicol Suppl 9, 1986; 154–158.PubMedCrossRefGoogle Scholar
  9. 9.
    Furlong C.E., Richter R.J., Chapline C. and Crabb J.W. Purification of Rabbit and Human Serum Paraoxonase. Biochem. 30, 1991; 10133–10140.CrossRefGoogle Scholar
  10. 10.
    Blatter M-C., James R.W., Messmer S., Barja F. and Pometta D. Identification of a distinct human high-density lipoprotein subspecies defined by a lipoprotein-associated protein, K-85. Eur. J. Biochem 211, 1993; 871–879.Google Scholar
  11. 11.
    Mackness M.I., Walker C.H. and Carlson L.A. Low ‘A’-esterase activity in the serum of patients with fish-eye disease. Clin. Chem. 33, 1979; 587–588.Google Scholar
  12. 12.
    Mackness M.I., Peuchant E., Dumon M-F, Walker C.H. and Clerc M. Absence of ‘A’-esterase activity in the serum of a patient with Tangier diseaseClin. Biochem. 22, 1989; 475–478.Google Scholar
  13. 13.
    Mackness M.I., Harty D., Bhatnagar D., Winocour P.H., Arrol S., Ishola M. and Durrington P.N. Serum paraoxonase activity in FH and IDDM. Atherosclerosis 86, 1991; 193–199.PubMedCrossRefGoogle Scholar
  14. 14.
    McElveen J., Mackness M.I., Colley C.M., Peard T., Warner S. and Walker C.H. Distribution of paraoxonase hydrolytic activity in the serum of patients following myocardial infarction. Clin. Chem. 32, 1986; 671–673.PubMedGoogle Scholar
  15. 15.
    Durrington P.N. Hyperlipidaemia: Diagnosis and Management. Wright, London. 1989.Google Scholar
  16. 16.
    Steinberg D., Parthasarathy S., Carew T.E., Khoo J.C. and Witztum J.L. Beyond cholesterol-modifications to low-density lipoprotein that increase its atherogenicity. New Eng. J. Med. 320, 1989; 915–924.CrossRefGoogle Scholar
  17. 17.
    Witztum J.L. and Steinberg D. J. Role of oxidised low-density lipoprotein in atherogenesis Clin. Invest. 88, 1991; 1785–1792.CrossRefGoogle Scholar
  18. 18.
    Esterbauer H., Gebicki J., Puhl J. and Jurgens G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Rad. Biol. Med. 13, 1992; 341–390.Google Scholar
  19. 19.
    Regnstrom J., Nilsson J., Toruvall P., Laudou C. and Hamsten A. Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man. Lancet 339, 1992; 1183–1186.PubMedCrossRefGoogle Scholar
  20. 20.
    Babiy A.V., Gebicki J.M., Sullivan D.R. and Willey K. Increased oxidisability of plasma lipoproteins in diabetic patients can be decreased by probucol therapy and is not due to glycation. Biochem. Pharmacol 43, 1992; 995–1000.PubMedCrossRefGoogle Scholar
  21. 21.
    Assmann G., Schulbe H., Fune H. von Eckardstein A. and Seedorf U. In Miller N.E. (ed) High-density lipoproteins, reverse cholesterol transport and coronary artery disease. Amsterdam. Exerpta Medica 1989; 46–59.Google Scholar
  22. 22.
    Mackness, M.I., Arrol S. and Durrington P.N. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein.FEBS Letts. 286, 1991; 151–154.Google Scholar
  23. 23.
    Parthasarathy S., Barnett J. and Fong L.G. High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. Biochem. Biophys. Acta 1044, 1990; 275–283.CrossRefGoogle Scholar
  24. 24.
    Ohta T., Takata S., Morino Y. and Matesuda I. Protective effect of lipoproteins containing apoprotein A-I on Cu2+ catalysed oidation of human low density lipoproteinFEBS Letts. 257, 1989; 435–438.CrossRefGoogle Scholar
  25. 25.
    Navab M., Imes S.S., Hama S.Y., Hough G.P., Ross L.A., Bork R.W., Valentine A.J., Berliner J.A., Drinkwater D.C., Laks H. and Fogelman A.M. Monocyte transmigration induced by modification of low-density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high-density lipoprotein. J. Clin. Invest. 88, 1991; 2039–2046.PubMedCrossRefGoogle Scholar
  26. 26.
    Mackness, M.I., Abbott, C.A, Arrol S. and Durrington P.N. The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem. J. 1993, in press.Google Scholar
  27. 27.
    Mackness, M.I., Arrol S., Abbott, C.A., and Durrington P.N. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993, in press.Google Scholar
  28. 28.
    Lunec J. and Blake D. In: Cohen R.D., Lewis B., Alberti K.G.M.M. and Denmar A.M. (eds) The Metabolic and Molecular Basis of Acquired Disease (Vol 2 ). Bailliere Tindall, London. 1990; 189–212Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Michael I. Mackness
    • 1
  1. 1.University Department of MedicineManchester Royal InfirmaryManchesterUK

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