Myeloperoxidase (MPO) catalyzes oxidation of nitrite to nitrogen dioxide

Stable Identifier
R-HSA-8933635
Type
Reaction [transition]
Species
Homo sapiens
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Nitrite (NO2-) is the primary metabolic end product of nitric oxide (NO) that is produced by a wide variety of cell types by nitric oxide synthases (Knowles RG & Moncada S 1994). During inflammatory processes activated polymorphonuclear leukocytes are capable of converting physiological levels of nitrite (NO2-) into nitrogen dioxide (NO2) through the catalytic action of myeloperoxidase (MPO) (Van der Vliet A et al. 1997; Eiserich JP et al 1998; Burner U et al. 2000). Competition studies have demonstrated that MPO-dependent NO2- oxidation occurs in the presence of alternative anionic substrates (e.g. Cl-, Br, SCNT) suggesting that nitrite itself is a physiological substrate of mammalian peroxidase (Van der Vliet A et al. 1997). Nitrogen dioxide (NO2) can contribute to nitration of aromatic substrates such as tyrosine residue and 4-hydroxyphenyl acetic acid (HPA) during inflammatory processes (Sampson JB et al. 1998, Van der Vliet A et al. 1997; Eiserich JP et al 1998).

In the presence of hydrogen peroxide (H2O2) MPO can catalyze both one- and two-electron oxidations (Davies MJ 2011). Generally, ferric or native MPO reacts with H2O2 forming intemediate compound I (MPO-I). This redox intermediate is known to oxidize halides via a single two-electron reaction to produce the respective hypohalous acids and regenerate the native enzyme. Alternatively, stepwise reduction of compound I by two donor-derived electrons produces compound II (MPO-II) and subsequently the resting ferric state. Mechanistic studies have demonstrated that nitrite acts as an electron donor and reacts with compounds I to yield nitrogen dioxide (NO2) and compaund II. Subsequently, an additional nitrite molecule reduces compound II by one electron to regenerate a native state of MPO and to produce a second NO2 molecule (Burner U et al. 2000; Cape JC & Hurst JK 2009).

Literature References
PubMed ID Title Journal Year
19402211 The role of nitrite ion in phagocyte function--perspectives and puzzles

Cape, JL, Hurst, JK

Arch. Biochem. Biophys. 2009
21297906 Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention

Davies, MJ

J Clin Biochem Nutr 2011
10777476 Mechanism of reaction of myeloperoxidase with nitrite

Burner, U, Furtmuller, PG, Kettle, AJ, Koppenol, WH, Obinger, C

J. Biol. Chem. 2000
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Catalyst Activity
Title
peroxidase activity of MPO:ferriheme [phagocytic vesicle lumen]
Physical Entity
Activity
Orthologous Events
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