Biochemistry (Moscow)

, Volume 74, Issue 10, pp 1059–1069 | Cite as

Critical evaluation of toxic versus beneficial effects of methylglyoxal

Review

Abstract

In various organisms, an array of enzymes is involved in the synthesis and breakdown of methylglyoxal. Through these enzymes, it is intimately linked to several other physiologically important metabolites, suggesting that methylglyoxal has some important role to play in the host organism. Several in vitro and in vivo studies showed that methylglyoxal acts specifically against different types of malignant cells. These studies culminated in a recent investigation to evaluate a methylglyoxal-based formulation in treating a small group of cancer patients, and the results were promising. Methylglyoxal acts against a number of pathogenic microorganisms. However, recent literature abounds with the toxic effects of methylglyoxal, which are supposed to be mediated through methylglyoxal-derived advanced glycation end products (AGE). Many diseases such as diabetes, cataract formation, hypertension, and uremia are proposed to be intimately linked with methylglyoxal-derived AGE. However methylglyoxal-derived AGE formation and subsequent pathogenesis might be a very minor event because AGE are nonspecific reaction products that are derived through the reactions of carbonyl groups of reducing sugars with amino groups present in the side chains of lysine and arginine and in terminal amino groups of proteins. Moreover, the results of some in vitro experiments with methylglyoxal under non-physiological conditions were extrapolated to the in vivo situation. Some experiments even showed contradictory results and were differently interpreted. For this reason conclusions about the potential beneficial effects of methylglyoxal have often been neglected, thus hindering the advancement of medical science and causing some confusion in fundamental understanding. Overall, the potential beneficial effects of methylglyoxal far outweigh its possible toxic role in vivo, and it should be utilized for the benefit of suffering humanity.

Key words

methylglyoxal advanced glycation end products glucose cancer antiviral 

Abbreviations

AGE

advanced glycation end products

3-DG

3-deoxyglucosone

HbA1c

glycated hemoglobin

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cooper, R. A. (1984) Annu. Rev. Microbiol., 38, 49–68.CrossRefPubMedGoogle Scholar
  2. 2.
    Ray, M., and Ray, S. (1998) Curr. Sci., 75, 103–113.Google Scholar
  3. 3.
    Kalapos, M. P. (1999) Toxicol. Lett., 110, 145–175.CrossRefPubMedGoogle Scholar
  4. 4.
    Ewaschuk, J. B., Naylor, J. M., and Zello, G. A. (2005) J. Nutr., 135, 1619–1625.PubMedGoogle Scholar
  5. 5.
    Szent-Gyorgyi, A. (1979) Ciba Found. Symp., 67, 3–18.Google Scholar
  6. 6.
    De Bock, C. A., Brug, J., and Walop, J. N. (1957) Nature, 179, 706–707.CrossRefGoogle Scholar
  7. 7.
    French, F. A., and Freedlander, B. L. (1958) Cancer Res., 18, 172–175.PubMedGoogle Scholar
  8. 8.
    Pavlovic-Djuranovic, S., Kun, J. F., Schultz, J. E., and Beitz, E. (2006) Biochim. Biophys. Acta, 1758, 1012–1017.CrossRefPubMedGoogle Scholar
  9. 9.
    Rachman, H., Kim, N., Ulrichs, T., Baumann, S., Pradl, L., Nasser, E. A., Bild, M., Rother, M., Kuban, R. J., Lee, J. S., Hurwitz, R., Brinkmann, V., Kosmiadi, G. A., and Kaufmann, S. H. (2006) PLoS ONE, 1, e29.CrossRefPubMedGoogle Scholar
  10. 10.
    Mavric, E., Wittmann, S., Barth, G., and Henle, T. (2008) Mol. Nutr. Food Res., 52, 483–489.CrossRefPubMedGoogle Scholar
  11. 11.
    Egyud, L. G., and Szent-Gyorgyi, A. (1968) Science, 160, 1140.CrossRefPubMedGoogle Scholar
  12. 12.
    Conroy, P. J. (1979) Ciba Found. Symp., 67, 271–300.Google Scholar
  13. 13.
    Apple, M. A., and Greenberg, D. M. (1967) Cancer Chemother. Rep., 51, 455–464.Google Scholar
  14. 14.
    Grandhee, S. K., and Monnier, V. M. (1991) J. Biol. Chem., 266, 11649–11653.PubMedGoogle Scholar
  15. 15.
    Niwa, T., Katsuzaki, T., Miyazaki, S., Miyazaki, T., Ishizaki, Y., Hayase, F., Tatemichi, N., and Takei, Y. (1997) J. Clin. Invest., 99, 1272–1280.CrossRefPubMedGoogle Scholar
  16. 16.
    Wilker, S. C., Chellan, P., Arnold, B. M., and Nagaraj, R. H. (2001) Anal. Biochem., 290, 353–358.CrossRefPubMedGoogle Scholar
  17. 17.
    Biemel, K. M., Friedl, D. A., and Lederer, M. (2002) J. Biol. Chem., 277, 24907–24915.CrossRefPubMedGoogle Scholar
  18. 18.
    Sell, D. R., Biemel, K. M., Reihl, O., Lederer, M. O., Strauch, C. M., and Monnier, V. M. (2005) J. Biol. Chem., 280, 12310–12315.CrossRefPubMedGoogle Scholar
  19. 19.
    Odani, H., Shinzato, T., Matsumoto, Y., Usami, J., and Maeda, K. (1999) Biochem. Biophys. Res. Commun., 256, 89–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Nemet, I., Turk, Z., Duvnjak, L., Car, N., and Varga-Defterdarovic, L. (2005) Clin. Biochem., 38, 379–383.CrossRefPubMedGoogle Scholar
  21. 21.
    Lapolla, A., Reitano, R., Seraglia, R., Sartore, G., Ragazzi, E., and Traldi, P. (2005) Mol. Nutr. Food Res., 49, 685–690.CrossRefPubMedGoogle Scholar
  22. 22.
    Beisswenger, P. J., Howell, S. K., Touchette, A. D., Lal, S., and Szwergold, B. S. (1999) Diabetes, 48, 198–202.CrossRefPubMedGoogle Scholar
  23. 23.
    Chang, T., and Wu, L. (2006) Can. J. Physiol. Pharmacol., 84, 1229–1238.CrossRefPubMedGoogle Scholar
  24. 24.
    Thornalley, P. J. (2008) Drug Metab. Drug Interact., 23, 125–150.Google Scholar
  25. 25.
    Gao, Y., and Wang, Y. (2006) Biochemistry, 45, 15654–15660.CrossRefPubMedGoogle Scholar
  26. 26.
    Kumar, M. S., Reddy, P. Y., Kumar, P. A., Surolia, I., and Reddy, G. B. (2004) Biochem. J., 379, 273–282.CrossRefPubMedGoogle Scholar
  27. 27.
    Haik, G. M., Jr., Lo, T. W., and Thronalley, P. J. (1994) Exp. Eye Res., 59, 497–500.CrossRefPubMedGoogle Scholar
  28. 28.
    Chellan, P., and Nagaraj, R. H. (1999) Arch. Biochem. Biophys., 368, 98–104.CrossRefPubMedGoogle Scholar
  29. 29.
    Riley, M. L., and Harding, J. J. (1995) Biochim. Biophys. Acta, 1270, 36–43.PubMedGoogle Scholar
  30. 30.
    Monnier, V. M., and Cerami, A. (1981) Science, 211, 491–493.CrossRefPubMedGoogle Scholar
  31. 31.
    Tessier, F., Obrenovich, M., and Monnier, V. M. (1999) J. Biol. Chem., 274, 20796–20804.CrossRefPubMedGoogle Scholar
  32. 32.
    Szwergold, B. S., Kappler, F., and Brown, T. R. (1990) Science, 247, 451–454.CrossRefPubMedGoogle Scholar
  33. 33.
    McPherson, J. D., Shilton, B. H., and Walton, D. J. (1998) Biochemistry, 22, 1901–1907.Google Scholar
  34. 34.
    Nagaraj, R. H., Oya-Ito, T., Padayatti, P. S., Kumar, R., Mehta, S., West, K., Levison, B., Sun, J., Crabb, J. W., and Padival, A. K. (2003) Biochemistry, 42, 10746–10755.CrossRefPubMedGoogle Scholar
  35. 35.
    Denis, U., Lecomte, M., Paget, C., Ruggiero, D., Wiernsperger, N., and Lagarde, M. (2002) Free Radic. Biol. Med., 33, 236–247.CrossRefPubMedGoogle Scholar
  36. 36.
    Liu, B., Bhat, M., Padival, A. K., Smith, D. G., and Nagaraj, R. H. (2004) Invest. Ophthalmol. Vis. Sci., 45, 1983–1995.CrossRefPubMedGoogle Scholar
  37. 37.
    Kim, J., Son, J. W., Lee, J. A., Oh, Y. S., and Shinn, S. H. (2004) J. Korean Med. Sci., 19, 95–100.CrossRefPubMedGoogle Scholar
  38. 38.
    Fosmark, D. S., Torjesen, P. A., Kilhovd, B. K., Berg, T. J., Sandvik, L., Hanssen, K. F., Agardh, C. D., and Agardh, E. (2006) Metabolism, 55, 232–236.CrossRefPubMedGoogle Scholar
  39. 39.
    Cikamatana, L., Mitchell, P., Rochtchina, E., Foran, S., and Wang, J. J. (2007) Eye, 21, 465–471.PubMedGoogle Scholar
  40. 40.
    Varma, R., Macias, G. L., Torres, M., Klein, R., Pena, F. Y., and Azen, S. P. (2007) Ophthalmology, 114, 1332–1340.CrossRefPubMedGoogle Scholar
  41. 41.
    Wong, T., and Mitchell, P. (2007) Lancet, 369, 425–435.CrossRefPubMedGoogle Scholar
  42. 42.
    Gao, B. B., Clermont, A., Rook, S., Fonda, S. J., Srinivasan, V. J., Wojtkowski, M., Fujimoto, J. G., Avery, R. L., Arrigg, P. G., Bursell, S. E., Aiello, L. P., and Feener, F. P. (2007) Nature Med., 13, 181–188.CrossRefPubMedGoogle Scholar
  43. 43.
    Shelton, M. D., Kern, T. S., and Mieyal, J. J. (2007) J. Biol. Chem., 282, 12467–12474.CrossRefPubMedGoogle Scholar
  44. 44.
    Ola, M. S., Berkich, D. A., Xu, Y., King, M. T., Gardner, T. W., Simpson, I., and Lanonue, K. F. (2006) Am. J. Physiol. Endocrinol. Metab., 290, E1057–1067.CrossRefPubMedGoogle Scholar
  45. 45.
    Gomes, R., Sousa, S. M., Quintas, A., Cordeiro, C., Freire, A., Pereira, P., Martins, A., Monteiro, E., Barroso, E., and Ponces, F. A. (2005) Biochem. J., 385, 339–345.CrossRefPubMedGoogle Scholar
  46. 46.
    Lapolla, A., Flamini, R., Lupo, A., Arico, N. C., Rugiu, C., Reitano, R., Tubaro, M., Ragazzi, E., Seragila, R., and Traldi, P. (2005) Ann. N. Y. Acad. Sci., 1043, 217–224.CrossRefPubMedGoogle Scholar
  47. 47.
    Mortier, S., Faict, D., Schalkwijk, C. G., Lameire, N. H., and de Vriese, A. S. (2004) Kidney Int., 66, 1257–1265.CrossRefPubMedGoogle Scholar
  48. 48.
    Catalan, M. P., Santamaria, B., Reyero, A., Ortiz, A., Egido, J., and Ortiz, A. (2005) Kidney Int., 68, 1303–1311.CrossRefPubMedGoogle Scholar
  49. 49.
    Ortiz, A., Wieslander, A., Linden, T., Santamaria, B., Sanz, A., Justo, P., Sanchez-Nino, M. D., Benito, A., and Kjellstrand, P. (2006) Curr. Med. Chem., 13, 2695–2702.CrossRefPubMedGoogle Scholar
  50. 50.
    Erixon, M., Linden, T., Kjellstrand, P., Carlsson, O., Ernebrant, M., Forsback, G., Wieslander, A., and Jonsson, J. A. (2004) Perit. Dial. Int., 24, 392–398.PubMedGoogle Scholar
  51. 51.
    Gomes, R. A., Oliveira, L. M., Silva, M., Ascenso, C., Quintas, A., Costa, G., Coelho, A. V., Sousa, S. M., Ferreira, A. E., Ponces, F. A., and Cordeiro, C. (2008) Biochem. J., 416, 317–326.CrossRefPubMedGoogle Scholar
  52. 52.
    Heath, M. M., Rixon, K. C., and Harding, J. J. (1996) Biochim. Biophys. Acta, 1315, 176–184.PubMedGoogle Scholar
  53. 53.
    Gomes, R. A., Miranda, H. V., Silva, M. S., Graca, G., Coelho, A. V., Ferreira, A. E., Cordeiro, C., and Freire, A. P. (2006) FEBS J., 273, 5273–5287.CrossRefPubMedGoogle Scholar
  54. 54.
    Miller, A. G., Smith, D. G., Bhat, M., and Nagaraj, R. H. (2006) J. Biol. Chem., 281, 11864–11871.CrossRefPubMedGoogle Scholar
  55. 55.
    Berlanga, J., Cibrian, D., Guillen, I., Freyre, F., Alba, J. S., Lopez-Saura, P., Merino, N., Aldama, A., Quintela, A. M., Triana, M. E., Montequin, J. F., Ajamieh, H., Urquiza, D., Ahmed, N., and Thronalley, P. J. (2005) Clin. Sci. (Lond.), 109, 83–95.Google Scholar
  56. 56.
    Ghosh, M., Talukdar, D., Ghosh, S., Bhattacharyya, N., Ray, M., and Ray, S. (2006) Toxicol. Appl. Pharmacol., 212, 45–58.CrossRefPubMedGoogle Scholar
  57. 57.
    Ray, M., Basu, N., and Ray, S. (1997) Mol. Cell. Biochem., 177, 21–26.CrossRefPubMedGoogle Scholar
  58. 58.
    Thronalley, P. J., Strath, M., and Wilson, R. J. (1994) Biochem. Pharmacol., 47, 418–420.CrossRefGoogle Scholar
  59. 59.
    Tiffany, B. D., Wright, J. B., Moffett, R. B., Heinzelman, R. V., Strube, R. E., Aspergren, B. D., Lincoln, E. H., and White, J. L. (1957) J. Am. Chem. Soc., 79, 1682–1687.CrossRefGoogle Scholar
  60. 60.
    Ghizatullina, N. K. (1976) Acta Virol., 20, 380–386.PubMedGoogle Scholar
  61. 61.
    Baylor, M. B., and Egyud, L. G. (1967) Virology, 31, 380–382.CrossRefPubMedGoogle Scholar
  62. 62.
    Apple, M. A., and Greenberg, D. M. (1968) Cancer Chemother. Rep., 52, 687–696.PubMedGoogle Scholar
  63. 63.
    Webster, J., Urban, C., Berbaum, K., Loske, C., Alpar, A., Gartner, U., de Arriba, S. G., Arendt, T., and Munch, G. (2005) Neurotox. Res., 7, 95–101.CrossRefPubMedGoogle Scholar
  64. 64.
    Ayoub, F. M., Allen, R. E., and Thornalley, P. J. (1993) Leuk. Res., 17, 397–401.CrossRefPubMedGoogle Scholar
  65. 65.
    Xu, Y., and Chen, X. (2006) J. Biol. Chem., 281, 26702–26713.CrossRefPubMedGoogle Scholar
  66. 66.
    Davidson, S. D., Milanesa, D. M., Mallouh, C., Choudhury, M. S., Tazaki, H., and Konno, S. (2002) Urol. Res., 30, 116–121.CrossRefPubMedGoogle Scholar
  67. 67.
    Rulli, A., Carli, L., Romani, R., Baroni, T., Giovannini, E., Rosi, G., and Talesa, V. (2001) Breast Cancer Res. Treat., 66, 67–72.CrossRefPubMedGoogle Scholar
  68. 68.
    Mearini, E., Romani, R., Mearini, L., Antognelli, C., Zucchi, A., Baroni, T., Porena, M., and Talesa, V. N. (2002) Eur. J. Cancer, 38, 1946–1950.CrossRefPubMedGoogle Scholar
  69. 69.
    Sakamoto, H., Mashima, T., Kizaki, A., Dan, S., Hashimoto, Y., Naito, M., and Tsuruo, T. (2000) Blood, 95, 3214–3218.PubMedGoogle Scholar
  70. 70.
    Di, I. C., Angelucci, S., Pennelli, A., Zezza, A., Tenaglia, R., and Sacchetta, P. (1995) Cancer Lett., 96, 189–193.CrossRefGoogle Scholar
  71. 71.
    Lieber, M. M. (1995) Forntier Perspect., 4, 35–41.Google Scholar
  72. 72.
    Roy, K., De, S., Ray, M., and Ray, S. (2004) Plant Growth Regul., 44, 33–45.CrossRefGoogle Scholar
  73. 73.
    Creighton, D. J., Zheng, Z. B., Holewinski, R., Hamilton, and Eiseman, J. L. (2003) Biochem. Soc. Trans., 31, 1378–1382.CrossRefPubMedGoogle Scholar
  74. 74.
    Santel, T., Pflug, G., Hemdan, N. Y., Schafer, A., Hollenbach, M., Buchold, M., Hintersdorf, A., Lindner, I., Otto, A., Bigl, M., Oerlecke, I., Hutschenreuter, A., Sack, U., Huse, K., Groth, M., Birkemeyer, C., Schellenberger, W., Gebhardt, R., Platzer, M., Weiss, T., Vijayalakshmi, M. A., Kruger, M., and Birkenmeier, G. (2008) PLoS ONE, 3, e3508.CrossRefPubMedGoogle Scholar
  75. 75.
    Ray, M., Halder, J., Dutta, S. K., and Ray, S. (1991) Int. J. Cancer, 47, 603–609.CrossRefPubMedGoogle Scholar
  76. 76.
    Biswas, S., Ray, M., Misra, S., Dutta, D. P., and Ray, S. (1997) Biochem. J., 323, 343–348.PubMedGoogle Scholar
  77. 77.
    Ray, S., Dutta, S., Halder, J., and Ray, M. (1994) Biochem. J., 303, 69–72.PubMedGoogle Scholar
  78. 78.
    Ray, S., Biswas, S., and Ray, M. (1997) Mol. Cell. Biochem., 171, 95–103.CrossRefPubMedGoogle Scholar
  79. 79.
    Ray, S., and Ray, M. (1997) Med. Hypothes., 48, 473–476.CrossRefGoogle Scholar
  80. 80.
    Ray, M., Ghosh, S., Kar, M., Datta, S., and Ray, S. (2001) Ind. J. Phys., 75B, 73–77.Google Scholar
  81. 81.
    Talukdar, D., Ray, S., Das, S., Jain, A. K., Kulkarni, A., and Ray, M. (2006) Cancer Therapy, 4, 205–222.Google Scholar
  82. 82.
    Talukdar, D., Ray, S., Ray, M., and Das, S. (2008) Drug Metab. Drug Interact., 23, 175–210.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  1. 1.Department of Biological ChemistryIndian Association for the Cultivation of ScienceJadavpur, KolkataIndia

Personalised recommendations