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

Research output: Contribution to journalJournal articleResearchpeer-review

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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. / Skaff, Ojia; Pattison, David I; Morgan, Philip E; Bachana, Rushad; Jain, Vimal K; Priyadarsini, K Indira; Davies, Michael Jonathan.

In: Biochemical Journal, Vol. 441, No. 1, 01.01.2012, p. 305-16.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Skaff, O, Pattison, DI, Morgan, PE, Bachana, R, Jain, VK, Priyadarsini, KI & Davies, MJ 2012, 'Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage', Biochemical Journal, vol. 441, no. 1, pp. 305-16. https://doi.org/10.1042/BJ20101762

APA

Skaff, O., Pattison, D. I., Morgan, P. E., Bachana, R., Jain, V. K., Priyadarsini, K. I., & Davies, M. J. (2012). Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage. Biochemical Journal, 441(1), 305-16. https://doi.org/10.1042/BJ20101762

Vancouver

Skaff O, Pattison DI, Morgan PE, Bachana R, Jain VK, Priyadarsini KI et al. Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage. Biochemical Journal. 2012 Jan 1;441(1):305-16. https://doi.org/10.1042/BJ20101762

Author

Skaff, Ojia ; Pattison, David I ; Morgan, Philip E ; Bachana, Rushad ; Jain, Vimal K ; Priyadarsini, K Indira ; Davies, Michael Jonathan. / Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid : determination of absolute rate constants and implications for biological damage. In: Biochemical Journal. 2012 ; Vol. 441, No. 1. pp. 305-16.

Bibtex

@article{63c2868564ec4b9fa89d5cb3f70af877,
title = "Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage",
abstract = "Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl-, Br- and SCN- by H2O2 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 H2O2, 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 ~5×105 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.",
keywords = "Amino Acids, Erythrocytes, Glutathione Peroxidase, Humans, Kinetics, Male, Molecular Structure, Oxidation-Reduction, Peroxidase, Selenium, Thiocyanates, Thioredoxin-Disulfide Reductase",
author = "Ojia Skaff and Pattison, {David I} and Morgan, {Philip E} and Rushad Bachana and Jain, {Vimal K} and Priyadarsini, {K Indira} and Davies, {Michael Jonathan}",
year = "2012",
month = "1",
day = "1",
doi = "10.1042/BJ20101762",
language = "English",
volume = "441",
pages = "305--16",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid

T2 - determination of absolute rate constants and implications for biological damage

AU - Skaff, Ojia

AU - Pattison, David I

AU - Morgan, Philip E

AU - Bachana, Rushad

AU - Jain, Vimal K

AU - Priyadarsini, K Indira

AU - Davies, Michael Jonathan

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl-, Br- and SCN- by H2O2 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 H2O2, 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 ~5×105 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.

AB - Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl-, Br- and SCN- by H2O2 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 H2O2, 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 ~5×105 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.

KW - Amino Acids

KW - Erythrocytes

KW - Glutathione Peroxidase

KW - Humans

KW - Kinetics

KW - Male

KW - Molecular Structure

KW - Oxidation-Reduction

KW - Peroxidase

KW - Selenium

KW - Thiocyanates

KW - Thioredoxin-Disulfide Reductase

U2 - 10.1042/BJ20101762

DO - 10.1042/BJ20101762

M3 - Journal article

C2 - 21892922

VL - 441

SP - 305

EP - 316

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

ER -

ID: 129669459