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Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin

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 con...

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Autores principales: Sueck, Franziska, Poór, Miklós, Faisal, Zelma, Gertzen, Christoph G. W., Cramer, Benedikt, Lemli, Beáta, Kunsági-Máté, Sándor, Gohlke, Holger, Humpf, Hans-Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070976/
https://www.ncbi.nlm.nih.gov/pubmed/29932113
http://dx.doi.org/10.3390/toxins10070256
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author Sueck, Franziska
Poór, Miklós
Faisal, Zelma
Gertzen, Christoph G. W.
Cramer, Benedikt
Lemli, Beáta
Kunsági-Máté, Sándor
Gohlke, Holger
Humpf, Hans-Ulrich
author_facet Sueck, Franziska
Poór, Miklós
Faisal, Zelma
Gertzen, Christoph G. W.
Cramer, Benedikt
Lemli, Beáta
Kunsági-Máté, Sándor
Gohlke, Holger
Humpf, Hans-Ulrich
author_sort Sueck, Franziska
collection PubMed
description 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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spelling pubmed-60709762018-08-09 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, Sándor Gohlke, Holger Humpf, Hans-Ulrich Toxins (Basel) Article 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. MDPI 2018-06-22 /pmc/articles/PMC6070976/ /pubmed/29932113 http://dx.doi.org/10.3390/toxins10070256 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sueck, Franziska
Poór, Miklós
Faisal, Zelma
Gertzen, Christoph G. W.
Cramer, Benedikt
Lemli, Beáta
Kunsági-Máté, Sándor
Gohlke, Holger
Humpf, Hans-Ulrich
Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin
title Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin
title_full Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin
title_fullStr Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin
title_full_unstemmed Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin
title_short Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin
title_sort interaction of ochratoxin a and its thermal degradation product 2′r-ochratoxin a with human serum albumin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070976/
https://www.ncbi.nlm.nih.gov/pubmed/29932113
http://dx.doi.org/10.3390/toxins10070256
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