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The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity
Antioxidants act as intermediates by picking up the high unselective reactivity of radicals and transferring it to other molecules. In this process the reactivity is reduced and becomes selective. This channeling of the reactivity can cause selective toxicity. The antioxidant quercetin is known to c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057684/ https://www.ncbi.nlm.nih.gov/pubmed/24786288 http://dx.doi.org/10.3390/ijms15057475 |
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author | Lemmens, Kristien J. A. Vrolijk, Misha F. Bouwman, Freek G. van der Vijgh, Wim J. F. Bast, Aalt Haenen, Guido R. M. M. |
author_facet | Lemmens, Kristien J. A. Vrolijk, Misha F. Bouwman, Freek G. van der Vijgh, Wim J. F. Bast, Aalt Haenen, Guido R. M. M. |
author_sort | Lemmens, Kristien J. A. |
collection | PubMed |
description | Antioxidants act as intermediates by picking up the high unselective reactivity of radicals and transferring it to other molecules. In this process the reactivity is reduced and becomes selective. This channeling of the reactivity can cause selective toxicity. The antioxidant quercetin is known to channel the reactivity towards thiol groups. The present study compares the thiol reactivity of quercetin with that of 4′O-methylquercetin (tamarixetin) towards creatine kinase (CK), a vital protein that contains a critical thiol moiety. Our results showed that oxidized quercetin and oxidized tamarixetin both adduct CK, which then loses its enzymatic function. Ascorbate, an important representative of the antioxidant network, is able to prevent adduction to and thus the inhibition of the enzyme by tamarixetin but not by quercetin. Apparently, tamarixetin is less thiol toxic than quercetin, because—rather than adduction to CK—tamarixetin quinone prefers to pass reactivity to the antioxidant network, i.e., to ascorbate. The findings exemplify that radical scavenging flavonoids pick up the reactivity of radicals and act as a pivot in directing the way the reactivity is channeled. A mere minor structural difference of only one methyl moiety between quercetin and tamarixetin appears to have a high impact on the selective, thiol toxicity. |
format | Online Article Text |
id | pubmed-4057684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-40576842014-06-16 The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity Lemmens, Kristien J. A. Vrolijk, Misha F. Bouwman, Freek G. van der Vijgh, Wim J. F. Bast, Aalt Haenen, Guido R. M. M. Int J Mol Sci Article Antioxidants act as intermediates by picking up the high unselective reactivity of radicals and transferring it to other molecules. In this process the reactivity is reduced and becomes selective. This channeling of the reactivity can cause selective toxicity. The antioxidant quercetin is known to channel the reactivity towards thiol groups. The present study compares the thiol reactivity of quercetin with that of 4′O-methylquercetin (tamarixetin) towards creatine kinase (CK), a vital protein that contains a critical thiol moiety. Our results showed that oxidized quercetin and oxidized tamarixetin both adduct CK, which then loses its enzymatic function. Ascorbate, an important representative of the antioxidant network, is able to prevent adduction to and thus the inhibition of the enzyme by tamarixetin but not by quercetin. Apparently, tamarixetin is less thiol toxic than quercetin, because—rather than adduction to CK—tamarixetin quinone prefers to pass reactivity to the antioxidant network, i.e., to ascorbate. The findings exemplify that radical scavenging flavonoids pick up the reactivity of radicals and act as a pivot in directing the way the reactivity is channeled. A mere minor structural difference of only one methyl moiety between quercetin and tamarixetin appears to have a high impact on the selective, thiol toxicity. Molecular Diversity Preservation International (MDPI) 2014-04-30 /pmc/articles/PMC4057684/ /pubmed/24786288 http://dx.doi.org/10.3390/ijms15057475 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Lemmens, Kristien J. A. Vrolijk, Misha F. Bouwman, Freek G. van der Vijgh, Wim J. F. Bast, Aalt Haenen, Guido R. M. M. The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity |
title | The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity |
title_full | The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity |
title_fullStr | The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity |
title_full_unstemmed | The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity |
title_short | The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity |
title_sort | minor structural difference between the antioxidants quercetin and 4′o-methylquercetin has a major impact on their selective thiol toxicity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057684/ https://www.ncbi.nlm.nih.gov/pubmed/24786288 http://dx.doi.org/10.3390/ijms15057475 |
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