Skip to main content
SpringerLink
Log in
Book cover

The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism pp 87–102Cite as

Paraoxonase 1 (PON1), A Junction Between the Metabolisms of Homocysteine and Lipids

  • Chapter

Part of the book series: Proteins And Cell Regulation ((PROR,volume 6))

Abstract

Homocysteine and cholesterol are linked to the development of atherothrombotic disease. Distinct homocysteine-specific and lipid-specific mechanisms contribute to the pathogenicity resulting from excesses of these metabolites. However, it is becoming increasingly clear that there are important interactions between the homocysteine and lipoprotein metabolic pathways. This article reviews evidence documenting interactions between metabolisms of homocysteine and high-density lipoproteins

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Refernces

  • Anderson, J.L., Muhlestein, J.B., Horne, B.D., Carlquist, J.F., Bair, T.L., Madsen, T.E., and Pearson, R.R., 2000, Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation, 102, 1227–32.

    CAS  PubMed  Google Scholar 

  • Beltowski, J., Wojcicka, G., and Jamroz, A., 2004, Effect of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins) on tissue paraoxonase 1 and plasma platelet activating factor acetylhydrolase activities. J Cardiovasc Pharmacol, 43, 121–7.

    Article  CAS  PubMed  Google Scholar 

  • Bonaa, K.H., Njolstad, I., Ueland, P.M., Schirmer, H., Tverdal, A., Steigen, T., Wang, H., Nordrehaug, J.E., Arnesen, E., and Rasmussen, K., 2006, Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med, 354, 1578–88.

    Article  CAS  PubMed  Google Scholar 

  • Chwatko, G., and Jakubowski, H., 2005a, Urinary excretion of homocysteine-thiolactone in humans. Clin Chem, 51, 408–15.

    Article  CAS  Google Scholar 

  • Chwatko, G., and Jakubowski, H., 2005b, The determination of homocysteine-thiolactone in human plasma. Anal Biochem, 337, 271–7.

    Article  CAS  Google Scholar 

  • Chwatko, G., Boers, G.H., Strauss, K.A., Shih, D.M., and Jakubowski, H., 2007, Mutations in methylenetetrahydrofolate reductase or cystathionine β-syntase gene and high methionine diet increase homocysteine-thiolactone levels in humans and mice. FASEB J, 21, in press.

    Google Scholar 

  • Clarke, R., Lewington, S., Sherliker, P., and Armitage, J., 2007, Effects of B-vitamins on plasma homocysteine concentrations and on risk of cardiovascular disease and dementia. Curr Opin Clin Nutr Metab Care, 10, 32–9.

    Article  PubMed  Google Scholar 

  • Connelly, P.W., Draganov, D., and Maguire, G.F., 2005, Paraoxonase-1 does not reduce or modify oxidation of phospholipids by peroxynitrite. Free Radic Biol Med, 38, 164–74.

    Article  CAS  PubMed  Google Scholar 

  • Deakin, S., Leviev, I., Guernier, S., and James, R.W., 2003, Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol, 23, 2083–9.

    Article  CAS  PubMed  Google Scholar 

  • Domagala, T.B., Lacinski, M., Trzeciak, W.H., Mackness, B., Mackness, M.I., and Jakubowski, H., 2006, The correlation of homocysteine-thiolactonase activity of the paraoxonase (PON1) protein with coronary heart disease status. Cell Mol Biol (Noisy-le-grand), 52, 3–9.

    Google Scholar 

  • Donahue, S., Struman, J.A., and Gaull, G., 1974, Arteriosclerosis due to homocyst (e) inemia. Failure to reproduce the model in weanling rabbits. Am J Pathol, 77, 167–3.

    CAS  PubMed  Google Scholar 

  • Endo, N., Nishiyama, K., Otsuka, A., Kanouchi, H., Taga, M., and Oka, T., 2006, Antioxidant activity of vitamin B6 delays homocysteine-induced atherosclerosis in rats. Br J Nutr, 95, 1088–93.

    Article  CAS  PubMed  Google Scholar 

  • Ferretti, G., Bacchetti, T., Moroni, C., Vignini, A., Nanetti, L., and Curatola, G., 2004, Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells. J Cell Biochem, 92, 351–60.

    Article  CAS  PubMed  Google Scholar 

  • Folbergrova, J., 1997, Anticonvulsant action of both NMDA and non-NMDA receptor antagonists against seizures induced by homocysteine in immature rats. Exp Neurol, 145, 442–50.

    Article  CAS  PubMed  Google Scholar 

  • Glowacki, R., and Jakubowski, H., 2004, Cross-talk between Cys34 and lysine residues in human serum albumin revealed by N-homocysteinylation. J Biol Chem, 279, 10864–71.

    Article  CAS  PubMed  Google Scholar 

  • Gouedard, C., Koum-Besson, N., Barouki, R., and Morel, Y., 2003, Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins. Mol Pharmacol, 63, 945–56.

    Article  CAS  PubMed  Google Scholar 

  • Greene, N.D., Dunlevy, L.E., and Copp, A.J., 2003, Homocysteine is embryotoxic but does not cause neural tube defects in mouse embryos. Anat Embryol (Berl), 206, 185–91.

    CAS  Google Scholar 

  • Hansen, D.K., Grafton, T.F., Melnyk, S., and James, S.J., 2001, Lack of embryotoxicity of homocysteine thiolactone in mouse embryos in vitro. Reprod Toxicol, 15, 239–44.

    Article  CAS  PubMed  Google Scholar 

  • Harker, L.A., Slichter, S.J., Scott, C.R., and Ross, R., 1974, Homocystinemia. Vascular injury and arterial thrombosis. N Engl J Med, 291, 537–43.

    Article  CAS  PubMed  Google Scholar 

  • Huang, R.F., Huang, S.M., Lin, B.S., Wei, J.S., and Liu, T.Z., 2001, Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci, 68, 2799–811.

    Article  CAS  PubMed  Google Scholar 

  • Jakubowski, H., 1991, Proofreading in vivo: editing of homocysteine by methionyl-tRNA synthetase in the yeast Saccharomyces cerevisiae. Embo J, 10, 593–8.

    CAS  PubMed  Google Scholar 

  • Jakubowski, H., 1997, Metabolism of homocysteine thiolactone in human cell cultures. Possible mechanism for pathological consequences of elevated homocysteine levels. J Biol Chem, 272, 1935–42.

    CAS  PubMed  Google Scholar 

  • Jakubowski, H., 1999, Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels. Faseb J, 13, 2277–83.

    CAS  PubMed  Google Scholar 

  • Jakubowski, H., 2000a, Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem, 275, 3957–62.

    Article  CAS  Google Scholar 

  • Jakubowski, H., Zhang, L., Bardeguez, A., and Aviv, A., 2000, Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: implications for atherosclerosis. Circ Res, 87, 45–51.

    CAS  PubMed  Google Scholar 

  • Jakubowski, H., 2000b, Homocysteine thiolactone: metabolic origin and protein homocysteinylation in humans. J Nutr, 130, 377S–81S.

    CAS  Google Scholar 

  • Jakubowski, H., 2001a, Biosynthesis and reactions of homocysteine thiolactone. In Homocysteine in Health and Disease (D. Jacobson, and R. Carmel, eds.), Cambridge University Press, Cambridge, UK, pp. 21–31.

    Google Scholar 

  • Jakubowski, H., 2001b, Translational accuracy of aminoacyl-tRNA synthetases: implications for atherosclerosis. J Nutr, 131, 2983S–7S.

    CAS  Google Scholar 

  • Jakubowski, H., Ambrosius, W.T., and Pratt, J.H., 2001, Genetic determinants of homocysteine thiolactonase activity in humans: implications for atherosclerosis. FEBS Lett, 491, 35–9.

    Article  CAS  PubMed  Google Scholar 

  • Jakubowski, H., 2002a, The determination of homocysteine-thiolactone in biological samples. Anal Biochem, 308, 112–9.

    Article  CAS  Google Scholar 

  • Jakubowski, H., 2002b, Homocysteine is a protein amino acid in humans. Implications for homocysteine-linked disease. J Biol Chem, 277, 30425–8.

    Article  CAS  Google Scholar 

  • Jakubowski, H., 2004, Molecular basis of homocysteine toxicity in humans. Cell Mol Life Sci, 61, 470–87.

    Article  CAS  PubMed  Google Scholar 

  • Jakubowski, H., 2005a, tRNA synthetase editing of amino acids. In Encyclopedia of Life Sciences, John Wiley & Sons, Ltd, Chichester, UK, p. http://www.els.net/doi:10.1038/npg.els.0003933.

    Google Scholar 

  • Jakubowski, H., 2005b, Accuracy of Aminoacyl-tRNA Synthetases: Proofreading of Amino Acids. In The Aminoacyl-tRNA Synthetases (M. Ibba, C. Francklyn, and S. Cusack, eds.), Landes Bioscience/Eurekah.com Georgetown, TX, pp. 384–96.

    Google Scholar 

  • Jakubowski, H., 2005c, Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease. Clin Chem Lab Med, 43, 1011–4.

    Article  CAS  Google Scholar 

  • Jakubowski, H., 2006a, Pathophysiological consequences of homocysteine excess. J Nutr, 136, 1741S–9S.

    CAS  Google Scholar 

  • Jakubowski, H., 2006b, Mechanism of the condensation of homocysteine thiolactone with aldehydes. Chemistry, 12, 8039–43.

    Article  CAS  Google Scholar 

  • James, R.W., 2006, A long and winding road: defining the biological role and clinical importance of paraoxonases. Clin Chem Lab Med, 44, 1052–9.

    Article  CAS  PubMed  Google Scholar 

  • Jarvik, G.P., Rozek, L.S., Brophy, V.H., Hatsukami, T.S., Richter, R.J., Schellenberg, G.D., and Furlong, C.E., 2000, Paraoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1(192) or PON1(55) genotype. Arterioscler Thromb Vasc Biol, 20, 2441–7.

    CAS  PubMed  Google Scholar 

  • Jarvik, G.P., Hatsukami, T.S., Carlson, C., Richter, R.J., Jampsa, R., Brophy, V.H., Margolin, S., Rieder, M., Nickerson, D., Schellenberg, G.D., Heagerty, P.J., and Furlong, C.E., 2003, Paraoxonase activity, but not haplotype utilizing the linkage disequilibrium structure, predicts vascular disease. Arterioscler Thromb Vasc Biol, 23, 1465–71.

    Article  CAS  PubMed  Google Scholar 

  • Kamudhamas, A., Pang, L., Smith, S.D., Sadovsky, Y., and Nelson, D.M., 2004, Homocysteine thiolactone induces apoptosis in cultured human trophoblasts: a mechanism for homocysteine-mediated placental dysfunction? Am J Obstet Gynecol, 191, 563–71.

    Article  CAS  PubMed  Google Scholar 

  • Kerkeni, M., Tnani, M., Chuniaud, L., Miled, A., Maaroufi, K., and Trivin, F., 2006, Comparative study on in vitro effects of homocysteine thiolactone and homocysteine on HUVEC cells: evidence for a stronger proapoptotic and proinflammative homocysteine thiolactone. Mol Cell Biochem, 291, 119–26.

    Article  CAS  PubMed  Google Scholar 

  • Khersonsky, O., and Tawfik, D.S., 2005, Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase. Biochemistry, 44, 6371–82.

    Article  CAS  PubMed  Google Scholar 

  • Kluijtmans, L.A., Boers, G.H., Kraus, J.P., van den Heuvel, L.P., Cruysberg, J.R., Trijbels, F.J., and Blom, H.J., 1999, The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment. Am J Hum Genet, 65, 59–67.

    Article  CAS  PubMed  Google Scholar 

  • Lacinski, M., Skorupski, W., Cieslinski, A., Sokolowska, J., Trzeciak, W.H., and Jakubowski, H., 2004, Determinants of homocysteine-thiolactonase activity of the paraoxonase-1 (PON1) protein in humans. Cell Mol Biol (Noisy-le-grand), 50, 885–93.

    CAS  Google Scholar 

  • Langmeier, M., Folbergrova, J., Haugvicova, R., Pokorny, J., and Mares, P., 2003, Neuronal cell death in hippocampus induced by homocysteic acid in immature rats. Epilepsia, 44, 299–304.

    Article  CAS  PubMed  Google Scholar 

  • Lawrence de Koning, A.B., Werstuck, G.H., Zhou, J., and Austin, R.C., 2003, Hyperhomocysteinemia and its role in the development of atherosclerosis. Clin Biochem, 36, 431–41.

    Article  CAS  PubMed  Google Scholar 

  • Lentz, S.R., 2005, Mechanisms of homocysteine-induced atherothrombosis. J Thromb Haemost, 3, 1646–54.

    Article  CAS  PubMed  Google Scholar 

  • Liao, D., Tan, H., Hui, R., Li, Z., Jiang, X., Gaubatz, J., Yang, F., Durante, W., Chan, L., Schafer, A.I., Pownall, H.J., Yang, X., and Wang, H., 2006, Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance. Circ Res, 99, 598–606.

    Article  CAS  PubMed  Google Scholar 

  • Lonn, E., Yusuf, S., Arnold, M.J., Sheridan, P., Pogue, J., Micks, M., McQueen, M.J., Probstfield, J., Fodor, G., Held, C., and Genest, J., Jr., 2006, Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med, 354, 1567–77.

    Article  CAS  PubMed  Google Scholar 

  • Mackness, B., Davies, G.K., Turkie, W., Lee, E., Roberts, D.H., Hill, E., Roberts, C., Durrington, P.N., and Mackness, M.I., 2001, Paraoxonase status in coronary heart disease: are activity and concentration more important than genotype? Arterioscler Thromb Vasc Biol, 21, 1451–7.

    Article  CAS  PubMed  Google Scholar 

  • Mackness, B., Durrington, P., McElduff, P., Yarnell, J., Azam, N., Watt, M., and Mackness, M., 2003, Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study. Circulation, 107, 2775–9.

    Article  CAS  PubMed  Google Scholar 

  • Mackness, M., Durrington, P., and Mackness, B., 2004a, Paraoxonase 1 activity, concentration and genotype in cardiovascular disease. Curr Opin Lipidol, 15, 399–404.

    Article  CAS  Google Scholar 

  • Mackness, M.I., Durrington, P.N., and Mackness, B., 2004b, The role of paraoxonase 1 activity in cardiovascular disease: potential for therapeutic intervention. Am J Cardiovasc Drugs, 4, 211–7.

    Article  CAS  Google Scholar 

  • Maestro de las Casas, C., Epeldegui, M., Tudela, C., Varela-Moreiras, G., and Perez-Miguelsanz, J., 2003, High exogenous homocysteine modifies eye development in early chick embryos. Birth Defects Res A Clin Mol Teratol, 67, 35–40.

    Google Scholar 

  • Makheja, A.N., Bombard, A.T., Randazzo, R.L., and Bailey, J.M., 1978, Anti-inflammatory drugs in experimental atherosclerosis. Part 3. Evaluation of the atherogenicity of homocystine in rabbits. Atherosclerosis, 29, 105–12.

    Article  CAS  PubMed  Google Scholar 

  • Marathe, G.K., Zimmerman, G.A., and McIntyre, T.M., 2003, Platelet-activating factor acetylhydrolase, and not paraoxonase-1, is the oxidized phospholipid hydrolase of high density lipoprotein particles. J Biol Chem, 278, 3937–47.

    Article  CAS  PubMed  Google Scholar 

  • McCully, K.S., 1969, Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol, 56, 111–28.

    CAS  PubMed  Google Scholar 

  • Mercie, P., Garnier, O., Lascoste, L., Renard, M., Closse, C., Durrieu, F., Marit, G., Boisseau, R.M., and Belloc, F., 2000, Homocysteine-thiolactone induces caspase-independent vascular endothelial cell death with apoptotic features. Apoptosis, 5, 403–11.

    Article  CAS  PubMed  Google Scholar 

  • Mikael, L.G., Genest, J., Jr., and Rozen, R., 2006, Elevated homocysteine reduces apolipoprotein A-I expression in hyperhomocysteinemic mice and in males with coronary artery disease. Circ Res, 98, 564–71.

    Article  CAS  PubMed  Google Scholar 

  • Mudd, S.H., Levy, H.L., and J.P., K., 2001, Disorders of transsulfuration. In The metabolic and Molecular Bases of Inherited Disease (C. Scriver, Beaudet al., Sly WS et al., eds.) Mc Graw-Hill, New York, Vol. 2, pp. 2007–56.

    Google Scholar 

  • Najib, S., and Sanchez-Margalet, V., 2005, Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol, 34, 119–26.

    Article  CAS  PubMed  Google Scholar 

  • Perla, J., Undas, A., Twardowski, T., and Jakubowski, H., 2004, Purification of antibodies against N-homocysteinylated proteins by affinity chromatography on Nomega-homocysteinyl-aminohexyl-Agarose. J Chromatogr B Analyt Technol Biomed Life Sci, 807, 257–61.

    Article  CAS  PubMed  Google Scholar 

  • Qujeq, D., Omran, T.S., and Hosini, L., 2001, Correlation between total homocysteine, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the serum of patients with myocardial infarction. Clin Biochem, 34, 97–101.

    Article  CAS  PubMed  Google Scholar 

  • Reuben, D.M., and Bruice, T.C., 1976, Reaction of thiol anions with benzene oxide and malachite green. J Am Chem Soc, 98, 114–21.

    Article  CAS  Google Scholar 

  • Robert, K., Chasse, J.F., Santiard-Baron, D., Vayssettes, C., Chabli, A., Aupetit, J., Maeda, N., Kamoun, P., London, J., and Janel, N., 2003, Altered gene expression in liver from a murine model of hyperhomocysteinemia. J Biol Chem, 278, 31504–11.

    Article  CAS  PubMed  Google Scholar 

  • Rosenblat, M., Gaidukov, L., Khersonsky, O., Vaya, J., Oren, R., Tawfik, D.S., and Aviram, M., 2006, The catalytic histidine dyad of high density lipoprotein-associated serum paraoxonase-1 (PON1) is essential for PON1-mediated inhibition of low density lipoprotein oxidation and stimulation of macrophage cholesterol efflux. J Biol Chem, 281, 7657–65.

    Article  CAS  PubMed  Google Scholar 

  • Rosenquist, T.H., Ratashak, S.A., and Selhub, J., 1996, Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid. Proc Natl Acad Sci U S A, 93, 15227–32.

    Article  CAS  PubMed  Google Scholar 

  • Roybal, C.N., Yang, S., Sun, C.W., Hurtado, D., Vander Jagt, D.L., Townes, T.M., and Abcouwer, S.F., 2004, Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem, 279, 14844–52.

    Article  CAS  PubMed  Google Scholar 

  • Rozek, L.S., Hatsukami, T.S., Richter, R.J., Ranchalis, J., Nakayama, K., McKinstry, L.A., Gortner, D.A., Boyko, E., Schellenberg, G.D., Furlong, C.E., and Jarvik, G.P., 2005, The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status. J Lipid Res, 46, 1888–95.

    Article  CAS  PubMed  Google Scholar 

  • Sass, J.O., Nakanishi, T., Sato, T., Sperl, W., and Shimizu, A., 2003, S-homocysteinylation of transthyretin is detected in plasma and serum of humans with different types of hyperhomocysteinemia. Biochem Biophys Res Commun, 310, 242–6.

    Article  CAS  PubMed  Google Scholar 

  • Sauls, D.L., Lockhart, E., Warren, M.E., Lenkowski, A., Wilhelm, S.E., and Hoffman, M., 2006, Modification of fibrinogen by homocysteine thiolactone increases resistance to fibrinolysis: a potential mechanism of the thrombotic tendency in hyperhomocysteinemia. Biochemistry, 45, 2480–7.

    Article  CAS  PubMed  Google Scholar 

  • Shih, D.M., Gu, L., Xia, Y.R., Navab, M., Li, W.F., Hama, S., Castellani, L.W., Furlong, C.E., Costa, L.G., Fogelman, A.M., and Lusis, A.J., 1998, Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature, 394, 284–7.

    Article  CAS  PubMed  Google Scholar 

  • Shih, D.M., Xia, Y.R., Wang, X.P., Miller, E., Castellani, L.W., Subbanagounder, G., Cheroutre, H., Faull, K.F., Berliner, J.A., Witztum, J.L., and Lusis, A.J., 2000, Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem, 275, 17527–35.

    Article  CAS  PubMed  Google Scholar 

  • Spence, A.M., Rasey, J.S., Dwyer-Hansen, L., Grunbaum, Z., Livesey, J., Chin, L., Nelson, N., Stein, D., Krohn, K.A., and Ali-Osman, F., 1995, Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates. Radiother Oncol, 35, 216–26.

    Article  CAS  PubMed  Google Scholar 

  • Spence, J.D., Bang, H., Chambless, L.E., and Stampfer, M.J., 2005, Vitamin Intervention For Stroke Prevention trial: an efficacy analysis. Stroke, 36, 2404–9.

    Article  CAS  PubMed  Google Scholar 

  • Stampfer, M.J., Malinow, M.R., Willett, W.C., Newcomer, L.M., Upson, B., Ullmann, D., Tishler, P.V., and Hennekens, C.H., 1992, A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. Jama, 268, 877–81.

    Article  CAS  PubMed  Google Scholar 

  • Stefani, M., 2004, Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world. Biochim Biophys Acta, 1739, 5–25.

    CAS  PubMed  Google Scholar 

  • Teiber, J.F., Draganov, D.I., and La Du, B.N., 2003, Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3. Biochem Pharmacol, 66, 887–96.

    Article  CAS  PubMed  Google Scholar 

  • Teiber, J.F., Draganov, D.I., and La Du, B.N., 2004, Purified human serum PON1 does not protect LDL against oxidation in the in vitro assays initiated with copper or AAPH. J Lipid Res, 45, 2260–8.

    Article  CAS  PubMed  Google Scholar 

  • Tomas, M., Senti, M., Garcia-Faria, F., Vila, J., Torrents, A., Covas, M., and Marrugat, J., 2000, Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients. Arterioscler Thromb Vasc Biol, 20, 2113–9.

    CAS  PubMed  Google Scholar 

  • Tward, A., Xia, Y.R., Wang, X.P., Shi, Y.S., Park, C., Castellani, L.W., Lusis, A.J., and Shih, D.M., 2002, Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation, 106, 484–90.

    Article  CAS  PubMed  Google Scholar 

  • Undas, A., Perla, J., Lacinski, M., Trzeciak, W., Kazmierski, R., and Jakubowski, H., 2004, Autoantibodies against N-homocysteinylated proteins in humans: implications for atherosclerosis. Stroke, 35, 1299–304.

    Article  CAS  PubMed  Google Scholar 

  • Undas, A., Jankowski, M., Twardowska, M., Padjas, A., Jakubowski, H., and Szczeklik, A., 2005, Antibodies to N-homocysteinylated albumin as a marker for early-onset coronary artery disease in men. Thromb Haemost, 93, 346–50.

    CAS  PubMed  Google Scholar 

  • Undas, A., Stepien, E., Glowacki, R., Tisonczyk, J., Tracz, W., and Jakubowski, H., 2006a, Folic acid administration and antibodies against homocysteinylated proteins in subjects with hyperhomocysteinemia. Thromb Haemost, 96, 342–7.

    CAS  Google Scholar 

  • Undas, A., Brozek, J., Jankowski, M., Siudak, Z., Szczeklik, A., and Jakubowski, H., 2006b, Plasma homocysteine affects fibrin clot permeability and resistance to lysis in human subjects. Arterioscler Thromb Vasc Biol, 26, 1397–404.

    Article  CAS  Google Scholar 

  • Van Aerts, L.A., Klaasboer, H.H., Postma, N.S., Pertijs, J.C., Peereboom, J.H., Eskes, T.K., and Noordhoek, J., 1993, Stereospecific in vitro embryotoxicity of L-homocysteine in pre- and post-implantation rodent embryos. Toxic in Vitro, 7, 743–9.

    Article  Google Scholar 

  • Wald, D.S., Law, M., and Morris, J.K., 2002, Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Bmj, 325, 1202.

    Article  PubMed  Google Scholar 

  • Yap, S., Boers, G.H., Wilcken, B., Wilcken, D.E., Brenton, D.P., Lee, P.J., Walter, J.H., Howard, P.M., and Naughten, E.R., 2001, Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study. Arterioscler Thromb Vasc Biol, 21, 2080–5.

    Article  CAS  PubMed  Google Scholar 

  • Zimny, J., Sikora, M., Guranowski, A., and Jakubowski, H., 2006, Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase. J Biol Chem, 281, 22485–92.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, 225 Warren Street, Newark, NJ 07101, USA

    H. Jakubowski

  2. Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznań, Poland

    H. Jakubowski

Authors
  1. H. Jakubowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Manchester, U.K

    Bharti Mackness

  2. University of Manchester, U.K

    Mike Mackness

  3. Technion Faculty of Medicine, Haifa, Israel

    Michael Aviram

  4. University of Debrecen, Hungary

    György Paragh

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer

About this chapter

Cite this chapter

Jakubowski, H. (2008). Paraoxonase 1 (PON1), A Junction Between the Metabolisms of Homocysteine and Lipids. In: Mackness, B., Mackness, M., Aviram, M., Paragh, G. (eds) The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism. Proteins And Cell Regulation, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6561-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4020-6561-3_6

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-1-4020-6560-6

  • Online ISBN: 978-1-4020-6561-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation