Reactions of myeloperoxidase-derived oxidants with biological substrates: Gaining chemical insight into human inflammatory diseases

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Reactions of myeloperoxidase-derived oxidants with biological substrates : Gaining chemical insight into human inflammatory diseases. / Pattison, D. I.; Davies, M. J.

In: Current Medicinal Chemistry, Vol. 13, No. 27, 2006, p. 3271-3290.

Research output: Contribution to journalReviewpeer-review

Harvard

Pattison, DI & Davies, MJ 2006, 'Reactions of myeloperoxidase-derived oxidants with biological substrates: Gaining chemical insight into human inflammatory diseases', Current Medicinal Chemistry, vol. 13, no. 27, pp. 3271-3290. https://doi.org/10.2174/092986706778773095

APA

Pattison, D. I., & Davies, M. J. (2006). Reactions of myeloperoxidase-derived oxidants with biological substrates: Gaining chemical insight into human inflammatory diseases. Current Medicinal Chemistry, 13(27), 3271-3290. https://doi.org/10.2174/092986706778773095

Vancouver

Pattison DI, Davies MJ. Reactions of myeloperoxidase-derived oxidants with biological substrates: Gaining chemical insight into human inflammatory diseases. Current Medicinal Chemistry. 2006;13(27):3271-3290. https://doi.org/10.2174/092986706778773095

Author

Pattison, D. I. ; Davies, M. J. / Reactions of myeloperoxidase-derived oxidants with biological substrates : Gaining chemical insight into human inflammatory diseases. In: Current Medicinal Chemistry. 2006 ; Vol. 13, No. 27. pp. 3271-3290.

Bibtex

@article{7404f45dca59461897a0c89123f43f21,
title = "Reactions of myeloperoxidase-derived oxidants with biological substrates: Gaining chemical insight into human inflammatory diseases",
abstract = "The heme enzyme myeloperoxidase (MPO) is released, at sites of inflammation by activated leukocytes. A key function of MPO is the production of hypohalous acids (HOX, X = Cl, Br) which are strong oxidants with potent antibacterial properties. However, HOX can also damage host tissue when produced at the wrong place, time or concentration; this has been implicated in several human diseases. Thus, elevated blood and leukocyte levels of MPO are significant independent risk factors for atherosclerosis, and specific markers of HOX-mediated protein oxidation are often present at elevated levels in patients with inflammatory diseases (e.g. asthma).HOX react readily with amino acids, proteins, carbohydrates, lipids, nucleobases and antioxidants. Sulfur-containing amino acids (Cys, Met, cystine) and amines on amino acids, nucleobases, sugars and lipids are the major targets for HOX. Reaction with amines generates chloramines (RNHCl) and bromamines (RNHBr), which are more selective oxidants than HOX and are key intermediates in HOX biochemistry. As these and other products of MPO-derived oxidants are unstable, understanding the role of HOX-induced damage in disease cannot be obtained solely by stable product analysis, and knowledge of the reaction kinetics is essential.This review collates kinetic and product data for HOX, chloramine and bromamine reactions with biological substrates. It highlights how kinetic data may be used to predict the effect of HOX-mediated oxidation on complex biological targets, such as lipoproteins and extracellular matrix in atherosclerosis, or protein-DNA complexes in cancer, thereby providing a basis for unraveling the mechanisms by which these oxidants generate biological damage.",
keywords = "myeloperoxidase, hypochlorous acid, hypobromous acid, chloramines, bromamines, kinetics, protein oxidation, lipid oxidation, LOW-DENSITY-LIPOPROTEIN, HYDROGEN-PEROXIDE-CHLORIDE, NITROGEN-CENTERED RADICALS, APOLIPOPROTEIN-A-I, HUMAN ATHEROSCLEROTIC LESIONS, HYPOCHLORITE-INDUCED DAMAGE, ALPHA-AMINO-ACIDS, ABCA1-DEPENDENT CHOLESTEROL EFFLUX, ABSOLUTE RATE CONSTANTS, GLYCATION END-PRODUCTS",
author = "Pattison, {D. I.} and Davies, {M. J.}",
year = "2006",
doi = "10.2174/092986706778773095",
language = "English",
volume = "13",
pages = "3271--3290",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers",
number = "27",

}

RIS

TY - JOUR

T1 - Reactions of myeloperoxidase-derived oxidants with biological substrates

T2 - Gaining chemical insight into human inflammatory diseases

AU - Pattison, D. I.

AU - Davies, M. J.

PY - 2006

Y1 - 2006

N2 - The heme enzyme myeloperoxidase (MPO) is released, at sites of inflammation by activated leukocytes. A key function of MPO is the production of hypohalous acids (HOX, X = Cl, Br) which are strong oxidants with potent antibacterial properties. However, HOX can also damage host tissue when produced at the wrong place, time or concentration; this has been implicated in several human diseases. Thus, elevated blood and leukocyte levels of MPO are significant independent risk factors for atherosclerosis, and specific markers of HOX-mediated protein oxidation are often present at elevated levels in patients with inflammatory diseases (e.g. asthma).HOX react readily with amino acids, proteins, carbohydrates, lipids, nucleobases and antioxidants. Sulfur-containing amino acids (Cys, Met, cystine) and amines on amino acids, nucleobases, sugars and lipids are the major targets for HOX. Reaction with amines generates chloramines (RNHCl) and bromamines (RNHBr), which are more selective oxidants than HOX and are key intermediates in HOX biochemistry. As these and other products of MPO-derived oxidants are unstable, understanding the role of HOX-induced damage in disease cannot be obtained solely by stable product analysis, and knowledge of the reaction kinetics is essential.This review collates kinetic and product data for HOX, chloramine and bromamine reactions with biological substrates. It highlights how kinetic data may be used to predict the effect of HOX-mediated oxidation on complex biological targets, such as lipoproteins and extracellular matrix in atherosclerosis, or protein-DNA complexes in cancer, thereby providing a basis for unraveling the mechanisms by which these oxidants generate biological damage.

AB - The heme enzyme myeloperoxidase (MPO) is released, at sites of inflammation by activated leukocytes. A key function of MPO is the production of hypohalous acids (HOX, X = Cl, Br) which are strong oxidants with potent antibacterial properties. However, HOX can also damage host tissue when produced at the wrong place, time or concentration; this has been implicated in several human diseases. Thus, elevated blood and leukocyte levels of MPO are significant independent risk factors for atherosclerosis, and specific markers of HOX-mediated protein oxidation are often present at elevated levels in patients with inflammatory diseases (e.g. asthma).HOX react readily with amino acids, proteins, carbohydrates, lipids, nucleobases and antioxidants. Sulfur-containing amino acids (Cys, Met, cystine) and amines on amino acids, nucleobases, sugars and lipids are the major targets for HOX. Reaction with amines generates chloramines (RNHCl) and bromamines (RNHBr), which are more selective oxidants than HOX and are key intermediates in HOX biochemistry. As these and other products of MPO-derived oxidants are unstable, understanding the role of HOX-induced damage in disease cannot be obtained solely by stable product analysis, and knowledge of the reaction kinetics is essential.This review collates kinetic and product data for HOX, chloramine and bromamine reactions with biological substrates. It highlights how kinetic data may be used to predict the effect of HOX-mediated oxidation on complex biological targets, such as lipoproteins and extracellular matrix in atherosclerosis, or protein-DNA complexes in cancer, thereby providing a basis for unraveling the mechanisms by which these oxidants generate biological damage.

KW - myeloperoxidase

KW - hypochlorous acid

KW - hypobromous acid

KW - chloramines

KW - bromamines

KW - kinetics

KW - protein oxidation

KW - lipid oxidation

KW - LOW-DENSITY-LIPOPROTEIN

KW - HYDROGEN-PEROXIDE-CHLORIDE

KW - NITROGEN-CENTERED RADICALS

KW - APOLIPOPROTEIN-A-I

KW - HUMAN ATHEROSCLEROTIC LESIONS

KW - HYPOCHLORITE-INDUCED DAMAGE

KW - ALPHA-AMINO-ACIDS

KW - ABCA1-DEPENDENT CHOLESTEROL EFFLUX

KW - ABSOLUTE RATE CONSTANTS

KW - GLYCATION END-PRODUCTS

U2 - 10.2174/092986706778773095

DO - 10.2174/092986706778773095

M3 - Review

VL - 13

SP - 3271

EP - 3290

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 27

ER -

ID: 314392702