Interaction of ochratoxin a and its thermal degradation product 2′R-ochratoxin a with human serum albumin

Franziska Sueck, Miklós Poór, Zelma Faisal, Christoph G.W. Gertzen, Benedikt Cramer, Beáta Lemli, S. Kunsági-Máté, Holger Gohlke, Hans Ulrich Humpf

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Ochratoxin A (OTA) is a toxic secondary metabolite produced by several fungal species of the genus Penicillium and Aspergillus. 2R-Ochratoxin A (2R-OTA) is a thermal isomerization product of OTA formed during food processing at high temperatures. Both compounds are detectable in human blood in concentrations between 0.02 and 0.41 µg/L with 2R-OTA being only detectable in the blood of coffee drinkers. Humans have approximately a fifty-fold higher exposure through food consumption to OTA than to 2R-OTA. In human blood, however, the differences between the concentrations of the two compounds is, on average, only a factor of two. To understand these unexpectedly high 2R-OTA concentrations found in human blood, the affinity of this compound to the most abundant protein in human blood the human serum albumin (HSA) was studied and compared to that of OTA, which has a well-known high binding affinity. Using fluorescence spectroscopy, equilibrium dialysis, circular dichroism (CD), high performance affinity chromatography (HPAC), and molecular modelling experiments, the affinities of OTA and 2R-OTA to HSA were determined and compared with each other. For the affinity of HSA towards OTA, a logK of 7.0–7.6 was calculated, while for its thermally produced isomer 2R-OTA, a lower, but still high, logK of 6.2–6.4 was determined. The data of all experiments showed consistently that OTA has a higher affinity to HSA than 2R-OTA. Thus, differences in the affinity to HSA cannot explain the relatively high levels of 2R-OTA found in human blood samples.

Original languageEnglish
Article number256
JournalToxins
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

Ochratoxins
Serum Albumin
Pyrolysis
Hot Temperature
Blood
ochratoxin A
Affinity chromatography
Coffee
Food processing
Food Handling
Molecular modeling
Dialysis
Aspergillus
Poisons
Penicillium
Fluorescence Spectrometry
Fluorescence spectroscopy
Metabolites
Isomerization
Circular Dichroism

Keywords

  • 2′R-ochratoxin A
  • Circular dichroism
  • Dialysis
  • Fluorescence spectroscopy
  • High performance affinity chromatography
  • Human serum albumin
  • Molecular modelling
  • Mycotoxin
  • Ochratoxin A

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Sueck, F., Poór, M., Faisal, Z., Gertzen, C. G. W., Cramer, B., Lemli, B., ... Humpf, H. U. (2018). Interaction of ochratoxin a and its thermal degradation product 2′R-ochratoxin a with human serum albumin. Toxins, 10(7), [256]. https://doi.org/10.3390/toxins10070256

Interaction of ochratoxin a and its thermal degradation product 2′R-ochratoxin a with human serum albumin. / Sueck, Franziska; Poór, Miklós; Faisal, Zelma; Gertzen, Christoph G.W.; Cramer, Benedikt; Lemli, Beáta; Kunsági-Máté, S.; Gohlke, Holger; Humpf, Hans Ulrich.

In: Toxins, Vol. 10, No. 7, 256, 01.07.2018.

Research output: Contribution to journalArticle

Sueck, F, Poór, M, Faisal, Z, Gertzen, CGW, Cramer, B, Lemli, B, Kunsági-Máté, S, Gohlke, H & Humpf, HU 2018, 'Interaction of ochratoxin a and its thermal degradation product 2′R-ochratoxin a with human serum albumin', Toxins, vol. 10, no. 7, 256. https://doi.org/10.3390/toxins10070256
Sueck, Franziska ; Poór, Miklós ; Faisal, Zelma ; Gertzen, Christoph G.W. ; Cramer, Benedikt ; Lemli, Beáta ; Kunsági-Máté, S. ; Gohlke, Holger ; Humpf, Hans Ulrich. / Interaction of ochratoxin a and its thermal degradation product 2′R-ochratoxin a with human serum albumin. In: Toxins. 2018 ; Vol. 10, No. 7.
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abstract = "Ochratoxin A (OTA) is a toxic secondary metabolite produced by several fungal species of the genus Penicillium and Aspergillus. 2′R-Ochratoxin A (2′R-OTA) is a thermal isomerization product of OTA formed during food processing at high temperatures. Both compounds are detectable in human blood in concentrations between 0.02 and 0.41 µg/L with 2′R-OTA being only detectable in the blood of coffee drinkers. Humans have approximately a fifty-fold higher exposure through food consumption to OTA than to 2′R-OTA. In human blood, however, the differences between the concentrations of the two compounds is, on average, only a factor of two. To understand these unexpectedly high 2′R-OTA concentrations found in human blood, the affinity of this compound to the most abundant protein in human blood the human serum albumin (HSA) was studied and compared to that of OTA, which has a well-known high binding affinity. Using fluorescence spectroscopy, equilibrium dialysis, circular dichroism (CD), high performance affinity chromatography (HPAC), and molecular modelling experiments, the affinities of OTA and 2′R-OTA to HSA were determined and compared with each other. For the affinity of HSA towards OTA, a logK of 7.0–7.6 was calculated, while for its thermally produced isomer 2′R-OTA, a lower, but still high, logK of 6.2–6.4 was determined. The data of all experiments showed consistently that OTA has a higher affinity to HSA than 2′R-OTA. Thus, differences in the affinity to HSA cannot explain the relatively high levels of 2′R-OTA found in human blood samples.",
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