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Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage

Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl(−), Br(−) and SCN(−) by H(2)O(2) to generate the powerful oxidants hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) respectively. The...

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Autores principales: Skaff, Ojia, Pattison, David I., Morgan, Philip E., Bachana, Rushad, Jain, Vimal K., Priyadarsini, K. Indira, Davies, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242511/
https://www.ncbi.nlm.nih.gov/pubmed/21892922
http://dx.doi.org/10.1042/BJ20101762
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author Skaff, Ojia
Pattison, David I.
Morgan, Philip E.
Bachana, Rushad
Jain, Vimal K.
Priyadarsini, K. Indira
Davies, Michael J.
author_facet Skaff, Ojia
Pattison, David I.
Morgan, Philip E.
Bachana, Rushad
Jain, Vimal K.
Priyadarsini, K. Indira
Davies, Michael J.
author_sort Skaff, Ojia
collection PubMed
description Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl(−), Br(−) and SCN(−) by H(2)O(2) to generate the powerful oxidants hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) respectively. These species are antibacterial agents, but misplaced or excessive production is implicated in tissue damage at sites of inflammation. Unlike HOCl and HOBr, which react with multiple targets, HOSCN targets cysteine residues with considerable selectivity. In the light of this reactivity, we hypothesized that Sec (selenocysteine) residues should also be rapidly oxidized by HOSCN, as selenium atoms are better nucleophiles than sulfur. Such oxidation might inactivate critical Sec-containing cellular protective enzymes such as GPx (glutathione peroxidase) and TrxR (thioredoxin reductase). Stopped-flow kinetic studies indicate that seleno-compounds react rapidly with HOSCN with rate constants, k, in the range 2.8×10(3)–5.8×10(6) M(−1)·s(−1) (for selenomethionine and selenocystamine respectively). These values are ~6000-fold higher than the corresponding values for H(2)O(2), and are also considerably larger than for the reaction of HOSCN with thiols (16-fold for cysteine and 80-fold for selenocystamine). Enzyme studies indicate that GPx and TrxR, but not glutathione reductase, are inactivated by HOSCN in a concentration-dependent manner; k for GPx has been determined as ~5×10(5) M(−1)·s(−1). Decomposed HOSCN did not induce inactivation. These data indicate that selenocysteine residues are oxidized rapidly by HOSCN, with this resulting in the inhibition of the critical intracellular Sec-dependent protective enzymes GPx and TrxR.
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spelling pubmed-32425112011-12-20 Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage Skaff, Ojia Pattison, David I. Morgan, Philip E. Bachana, Rushad Jain, Vimal K. Priyadarsini, K. Indira Davies, Michael J. Biochem J Research Article Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl(−), Br(−) and SCN(−) by H(2)O(2) to generate the powerful oxidants hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) respectively. These species are antibacterial agents, but misplaced or excessive production is implicated in tissue damage at sites of inflammation. Unlike HOCl and HOBr, which react with multiple targets, HOSCN targets cysteine residues with considerable selectivity. In the light of this reactivity, we hypothesized that Sec (selenocysteine) residues should also be rapidly oxidized by HOSCN, as selenium atoms are better nucleophiles than sulfur. Such oxidation might inactivate critical Sec-containing cellular protective enzymes such as GPx (glutathione peroxidase) and TrxR (thioredoxin reductase). Stopped-flow kinetic studies indicate that seleno-compounds react rapidly with HOSCN with rate constants, k, in the range 2.8×10(3)–5.8×10(6) M(−1)·s(−1) (for selenomethionine and selenocystamine respectively). These values are ~6000-fold higher than the corresponding values for H(2)O(2), and are also considerably larger than for the reaction of HOSCN with thiols (16-fold for cysteine and 80-fold for selenocystamine). Enzyme studies indicate that GPx and TrxR, but not glutathione reductase, are inactivated by HOSCN in a concentration-dependent manner; k for GPx has been determined as ~5×10(5) M(−1)·s(−1). Decomposed HOSCN did not induce inactivation. These data indicate that selenocysteine residues are oxidized rapidly by HOSCN, with this resulting in the inhibition of the critical intracellular Sec-dependent protective enzymes GPx and TrxR. Portland Press Ltd. 2011-12-14 2012-01-01 /pmc/articles/PMC3242511/ /pubmed/21892922 http://dx.doi.org/10.1042/BJ20101762 Text en © 2012 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Skaff, Ojia
Pattison, David I.
Morgan, Philip E.
Bachana, Rushad
Jain, Vimal K.
Priyadarsini, K. Indira
Davies, Michael J.
Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage
title Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage
title_full Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage
title_fullStr Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage
title_full_unstemmed Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage
title_short Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage
title_sort selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242511/
https://www.ncbi.nlm.nih.gov/pubmed/21892922
http://dx.doi.org/10.1042/BJ20101762
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