Myeloperoxidase (MPO) catalyzes oxidation of nitrite to nitrogen dioxide

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).<p>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).

亚硝酸盐（NO2-）是硝酸盐氧化酶（NOX）在多种细胞类型中产生的氧化氮（NO）的主要代谢终产物（Knowles RG & Moncada S, 1994）。在炎症过程中，激活的多形核白细胞能够通过髓过氧化物酶（MPO）的催化作用，将生理水平的亚硝酸盐（NO2-）转化为二氧化氮（NO2）（Van der Vliet A 等人，1997；Eiserich JP 等人，1998；Burner U 等人，2000）。竞争性研究表明，在存在替代阴离子底物（如Cl-、Br-、SCNT）的情况下，MPO依赖性NO2-氧化反应发生，这表明亚硝酸盐本身是哺乳动物过氧化物酶的生理底物（Van der Vliet A 等人，1997）。在炎症过程中，二氧化氮（NO2）可以参与酪氨酸残基和4-羟基苯乙酸（HPA）等芳香族底物的硝化作用（Sampson JB 等人，1998，Van der Vliet A 等人，1997；Eiserich JP 等人，1998）。在存在过氧化氢（H2O2）的情况下，MPO可以催化单电子和双电子氧化反应（Davies MJ，2011）。一般来说，铁或天然MPO与H2O2反应形成中间化合物I（MPO-I）。这种氧化还原中间体已知可以通过单电子反应氧化卤化物，生成相应的次卤酸和再生原始酶。另一方面，通过两个供体衍生的电子逐步还原化合物I，产生化合物II（MPO-II）并随后恢复为休息的铁状态。机制研究表明，亚硝酸盐作为电子供体与化合物I反应，生成二氧化氮（NO2）和化合物II。随后，另一个亚硝酸盐分子通过一个电子还原化合物II，以再生MPO的原始状态并产生第二个NO2分子（Burner U 等人，2000；Cape JC & Hurst JK，2009）。