Myeloperoxidase (MPO) produces hypochlorous acid (HOCl)

Stable Identifier
Reaction [transition]
Homo sapiens
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Phagosomal myeloperoxidase (MPO) is an important heme enzyme released by activated leukocytes (Klebanoff SJ & Rosen H 1978; Austin GE et al. 1994; Klebanoff S 2013). MPO protein has little bactericidal effect per se, but the enzyme-generated products are chemical oxidants that have potent antibacterial, antiviral, and antifungal properties (Pattison DI et al. 2012). Ferric MPO enzyme cycles through redox intermediates that undergo a complex array of reactions. Initial oxidation of the resting iron (III) form of the enzyme by hydrogen peroxide gives rise to a primary catalytic complex, known as Compound I (Winterbourn CC et al 2006; Davies MJ 2011; Pattison DI et al. 2012). Compound I can then undergo either two electron reduction with halide or pseudo-halide ions to form hypohalous acids (HOX where X = Cl, Br, SCN) or undergo two successive one-electron reductions, via Compound II, with consequent radical formation (the peroxidase cycle) (Winterbourn CC et al 2006; Davies MJ 2011). Due to the high reduction potentials of the Compound I and II, MPO can oxidize a variety of substrates. Chloride ion is one of the physiological substrate of MPO. Cl- undergoes a two-electron oxidation to form hypochlorous acid (HOCl) (Winterbourn CC et al 2006; Davies MJ 2001; Pattison DI et al. 2012). Studies using specific probes or biomarkers such as 3-chlorotyrosine showed that MPO reacts with H2O2 and chloride present in the phagosome to produce HOCl, and that the HOCl reacts with ingested bacteria (Jiang Q et al. 1997; Palazzolo AM et al. 2005; Kenmoku S et al. 2007; Chapman AL et al. 2002; Albrett AM et al. 2018; Degrossoli A et al. 2018). Furthermore, rapid killing of numerous organisms by isolated neutrophils has been shown to require MPO (Klebanoff SJ et al. 2013; Green JN et al. 2017). HOCl reacts readily with a range of biological molecules to form potently microbicidal products such as chloramines (Green JN et al. 2017). HOCl reacts with ROS forming toxic hydroxyl radical and singlet oxygen, however the specific role of HOCl in the microbial killing remains unclear. Modelling studies indicated that phagosomal proteins could scavenge much of the HOCl before it reaches the microbe thus limiting its ability to kill (Winterbourn CC et al. 2006).
Literature References
PubMed ID Title Journal Year
23066164 Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Rosen, H, Nauseef, WM, Winterbourn, CC, Kettle, AJ, Klebanoff, SJ

J. Leukoc. Biol. 2013
21297906 Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention

Davies, MJ

J Clin Biochem Nutr 2011
17074761 Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome: implications for microbial killing

Hampton, MB, Livesey, JH, Kettle, AJ, Winterbourn, CC

J. Biol. Chem. 2006
10766826 X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution

Fenna, RE, Fiedler, TJ, Davey, CA

J. Biol. Chem. 2000
22348603 Reactions and reactivity of myeloperoxidase-derived oxidants: differential biological effects of hypochlorous and hypothiocyanous acids

Hawkins, CL, Davies, MJ, Pattison, DI

Free Radic. Res. 2012
Catalyst Activity

peroxidase activity of MPO:ferriheme [phagocytic vesicle lumen]

Orthologous Events
Cross References
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