Acta Biologica Hungarica

, Volume 63, Issue 3, pp 389–398 | Cite as

Thermodynamic and Kinetic Processes during the Unfolding of BSA in the Presence of the Mycotoxin Patulin

  • Eszter Horváth
  • Nikoletta Kálmán
  • M. Pesti
  • K. Iwata
  • S. Kunsági-MátéEmail author


The effects of the mycotoxin patulin on the thermodynamics and kinetics of the transition of bovine serum albumin (BSA) in aqueous solution were studied by Differential Scanning Calorimetry and Photo-luminescence methods. Results show that in the presence of patulin, the free enthalpy change during the transition of BSA was decreased by an average of ~46 kJ/mol, the free energy change was decreased by ~4 kJ/mol, and the activation energy fell from ~1546 to -840 kJ/mol. These results indicate that the bioactivity of patulin is based on the kinetic rather than on the thermodynamic properties of the transition. This is the first evidence of the direct interaction of patulin with the free thiol-containing BSA, a process which could contribute to the adverse cyto- and genotoxic effects induced by patulin.


Patulin BSA unfolding transition thermodynamics and kinetics free enthalpy activation energy 



bovine serum albumin




transition temperature






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  1. 1.
    Benesi, H., Hildebrand, J. H. (1949) A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. Am. Chem. Soc. 71, 2703–2707.CrossRefGoogle Scholar
  2. 2.
    Bennett, J. W., Klich, M. (2003) Mycotoxins. Clin. Microbiol. Rev. 16, 497–516.CrossRefGoogle Scholar
  3. 3.
    Carter, D. C., Ho, J. X. (1994) Advances in protein chemistry. Academic Press Inc., San Diego.Google Scholar
  4. 4.
    Chiti, F., Taddei, N., Baronim, F., Capanni, C., Stefani, M., Ramponi, G., Dobson, C. M. (2002) Kinetic partitioning of protein unfolding and aggregation. Nat. Struct. Biol. 9, 137–143.CrossRefGoogle Scholar
  5. 5.
    Dombrink-Kurtzman, M. A., Blackburn, J. A. (2005) Evaluation of several culture media for production of patulin by Penicillium species. Int. J. Food Microbiol. 98, 241–248.CrossRefGoogle Scholar
  6. 6.
    Fliege, R., Metzler, M. (1999) The mycotoxin patulin induces intra- and intermolecular protein crosslinks in vitro involving cysteine, lysine, and histidine side chains, and a-amino groups. Chem. Biol Interact. 123, 85–103.CrossRefGoogle Scholar
  7. 7.
    Francis, G. L. (2010) Albumin and mammalian cell culture: implications for biotechnology applications. Cytotechnology 62, 1–16.Google Scholar
  8. 8.
    Giancola, C., De Sena, C., Fessas, D., Graziano, G., Barone, G. (1997) DSC studies on bovine serum albumin denaturation. Effects of ionic strength and SDS concentration. Int. J. Biol. Macromol. 20, 193–204.CrossRefGoogle Scholar
  9. 9.
    Horváth, E., Papp, G., Belágyi, J., Gazdag, Z., Vágvölgyi, C., Pesti, M. (2010) In vivo direct patulin-induced fluidization of the plasma membrane of fission yeast Schizosaccharomyces pombe. Food and Chem. Toxicol. 48, 1898–1904.CrossRefGoogle Scholar
  10. 10.
    Iwahashi, Y., Hosoda, H., Park, J. H., Lee, J. H., Suzuki, Y., Kitagawa, E., Murata, S. M., Jwa, N. S., Gu, M. B., Iwahashi, H. (2006) Mechanisms of patulin toxicity under conditions that inhibit yeast growth. J. Agric. Food Chem. 54, 1936–1942.CrossRefGoogle Scholar
  11. 11.
    Kissinger, H. E. (1957) Reaction kinetics in differential thermal analysis. Anal. Chem. 29, 1702–1706.CrossRefGoogle Scholar
  12. 12.
    Kunsági-Máté, S., Iwata, K. (2009) Effect of cluster formation of solvent molecules on the preferential solvatation of anthracene in binary alcoholic solutions. Chem. Phys. Lett. 473, 284–287.CrossRefGoogle Scholar
  13. 13.
    Kunsági-Máté, S., Kumar, A., Sharma, P., Kollár, L., Nikfardjam, M. P. (2009) Effect of molecular environment on the formation kinetics of complexes of malvidin-3-O-glucoside with caffeic acid and catechin. J. Phys. Chem. B113, 7468–7473.CrossRefGoogle Scholar
  14. 14.
    Kunsági-Máté, S., Lecomte, S., Ortmann, E., Kunsági-Máté, E., Desbat, B. (2010) The environment controlled effect of thiacalix[4]arene on the transition thermodynamics and kinetics of bovine serum albumin. J. Incl. Phenom. Macro. Chem. 66, 147–151.CrossRefGoogle Scholar
  15. 15.
    Kunsági-Máté, S., Csók, Zs., Iwata, K., Szász, E., Kollár, L. (2011) Role of the conformational freedom of the skeleton in the complex formation ability of resorcinarene derivatives toward a neutral phenol guest. J. Phys. Chem. B115, 3339–3343.CrossRefGoogle Scholar
  16. 16.
    Moriyama, Y., Watanabe, E., Kobayashi, K., Harano, H., Inui, E., Takeda, K. (2008) Secondary structural change of bovine serum albumin in thermal denaturation up to 130 °C and protective effect of sodium dodecyl sulfate on the change. J. Phys. Chem. B112, 16585–16589.CrossRefGoogle Scholar
  17. 17.
    Murillo, M., Gonzáles-Penas, E., Amezqueta, S. (2008) Determination of patulin in commercial apple juice by micellar electrokinetic chromatography. Food Chem. Toxicol. 46, 57–64.CrossRefGoogle Scholar
  18. 18.
    Privalov, P. L., Gill, S. J. (1988) Stability of protein structure and hydrophobic interaction. Advances in Protein Chemistry 39, 191–234.CrossRefGoogle Scholar
  19. 19.
    Privalov, P. L., Khechinashvili, N. N. (1974) A thermodynamic approach to the problem of stabilization of globular protein structure: A calorimetric study. J. Mol. Biol. 86, 665–684.CrossRefGoogle Scholar
  20. 20.
    Privalov, P. L., Dragan, A. I. (2007) Microcalorimetry of biological macromolecules. Biophys. Chem. 126, 16–24.CrossRefGoogle Scholar
  21. 21.
    Relkin, P., Mulvihill, D. M. (1996) Thermal unfolding of β-lactoglobulin, α-lactalbumin and bovine serum albumin. A thermodynamic approach. Critical Rev. Food Sci. and Nutrition 36, 565–601.Google Scholar
  22. 22.
    Ricelli, A., Baruzzi, F., Solfrizzo, M., Morea, M., Fanizzi, F. P. (2007) Biotransformation of patulin by Gluconobacter oxydons. Appl. Environ. Microbiol. 73, 785–792.CrossRefGoogle Scholar
  23. 23.
    Schumacher, D. M., Metzler, M., Lehmann, L. (2005) Mutagenicity of the mycotoxin patulin in cultured Chinese hamster V79 cells, and its modulation by intracellular glutathione. Arch. Toxicol. 79, 110–121.CrossRefGoogle Scholar
  24. 24.
    Tapia, M. O., Stern, M. D., Koski, R. L., Bach, A., Murphy, M. J. (2002) Effects of patulin on microbial fermentation in continuous culture fermenters. Animal Feed Sci. and Techn. 97, 239–246.CrossRefGoogle Scholar
  25. 25.
    Tong, G. C. (2003) Characterization of cysteine-34 in serum albumin. Thesis. The Ohio State Univ.Google Scholar
  26. 26.
    Virág, E., Pesti, M., Kunsági-Máté, S. (2010) Competitive hydrogen bonds associated with the effect of primycin antibiotic on oleic acid as a building block of plasma membranes. J. Antib. 63, 113–117.CrossRefGoogle Scholar

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© Akadémiai Kiadó, Budapest 2012

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Eszter Horváth
    • 1
  • Nikoletta Kálmán
    • 1
  • M. Pesti
    • 1
  • K. Iwata
    • 2
  • S. Kunsági-Máté
    • 3
    • 4
    Email author
  1. 1.Department of General and Environmental Microbiology, Faculty of SciencesUniversity of PécsPécsHungary
  2. 2.Department of Chemistry, Faculty of ScienceGakushuin UniversityTokyoJapan
  3. 3.Department of General and Physical Chemistry, Faculty of SciencesUniversity of PécsPécsHungary
  4. 4.János Szentágothai Research CenterPécsHungary

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