Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention

Abstract

There is considerable interest in the role that mammalian heme peroxidase enzymes, primarily myeloperoxidase, eosinophil peroxidase and lactoperoxidase, may play in a wide range of human pathologies. This has been sparked by rapid developments in our understanding of the basic biochemistry of these enzymes, a greater understanding of the basic chemistry and biochemistry of the oxidants formed by these species, the development of biomarkers that can be used damage induced by these oxidants in vivo, and the recent identification of a number of compounds that show promise as inhibitors of these enzymes. Such compounds offer the possibility of modulating damage in a number of human pathologies. This reviews recent developments in our understanding of the biochemistry of myeloperoxidase, the oxidants that this enzyme generates, and the use of inhibitors to inhibit such damage.

Keywords: chloramines; hypochlorous acid; myeloperoxidase; neutrophil; protein oxidation.

Fig. 1

The enzymatic cycles of myeloperoxidase. Initial oxidation of the resting iron (III) form of the enzyme by hydrogen peroxide gives rise to Compound I, which is formally an iron (V) species. This intermediate can then undergo either two electron reduction with halide or pseudohalide ions to form hypohalous acids (the halogenation cycle) or undergo two successive one-electron reductions, via Compound II, with consequent radical formation (the peroxidase cycle). The iron (III) form of the enzyme can alos undergo one electron reduction with superoxide radicals to give Compound III. This latter reaction accounts for the SOD mimetic activity of myeloperoxidase.