Myeloperoxidase Interactions with Nitric Oxide: A Review of Mechanistic Pathways

Myeloperoxidase (MPO), hemoprotein present in neutrophils and monocytes, has an essential role in immune surveillance and host defense mechanisms. Upon phagocyte activation in peripheral tissues and fluids, MPO is secreted into both the extracellular milieu and the phagolysosome where it uses hydrogen peroxide (H2O2) generated during a respiratory burst by activated NADPH as co-substrate. (Hurst, 1991) A kinetic model that describes the classic myeloperoxidase cycle is presented in Figure 1. The ground state (secreted) form of the enzyme, MPOFe(III), reacts in a rapid and reversible manner with H2O2 to form Compound I, a two e oxidized intermediate with Fe(IV)=O center and a resonance-stabilized porphyrin π cation radical with reduction potential of ~ -1.1 Volts ( Hurst, 1991). Compound I has the ability to oxidize chloride ion normally presented in biological systems (100mM) via a single two e oxidation forming hypochlorous acid (HOCl) (Harrison, and Schultz, 1976). HOCl has a potent macrobicidal and viricidal activity by playing the key role in protective and inflammatory responses in the host defense reaction (Albrich, McCarthy, and Hurst, 1981). In addition, Compound I may oxidize multiple available substrates through two sequential one e -