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Halogenation Activity of Mammalian Heme Peroxidases - PubMed

  • ️Sat Jan 01 2022

Review

Halogenation Activity of Mammalian Heme Peroxidases

Jürgen Arnhold et al. Antioxidants (Basel). 2022.

Abstract

Mammalian heme peroxidases are fascinating due to their unique peculiarity of oxidizing (pseudo)halides under physiologically relevant conditions. These proteins are able either to incorporate oxidized halides into substrates adjacent to the active site or to generate different oxidized (pseudo)halogenated species, which can take part in multiple (pseudo)halogenation and oxidation reactions with cell and tissue constituents. The present article reviews basic biochemical and redox mechanisms of (pseudo)halogenation activity as well as the physiological role of heme peroxidases. Thyroid peroxidase and peroxidasin are key enzymes for thyroid hormone synthesis and the formation of functional cross-links in collagen IV during basement membrane formation. Special attention is directed to the properties, enzymatic mechanisms, and resulting (pseudo)halogenated products of the immunologically relevant proteins such as myeloperoxidase, eosinophil peroxidase, and lactoperoxidase. The potential role of the (pseudo)halogenated products (hypochlorous acid, hypobromous acid, hypothiocyanite, and cyanate) of these three heme peroxidases is further discussed.

Keywords: cyanate; eosinophil peroxidase; hypobromous acid; hypochlorous acid; hypothiocyanite; lactoperoxidase; myeloperoxidase; peroxidasin; thyroid peroxidase.

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Conflict of interest statement

All authors declare no conflict of interest.

Figures

Figure 1
Figure 1

The role of the chloride–Compound I complex (CompI-Cl) in chlorination reactions mediated by MPO according to [44,45]. Explanations are given in the text. CompI denotes Compound I. AH2 represents a substrate that binds near the heme pocket. AHCl is the resulting chlorinated substrate.

Figure 2
Figure 2

Overview about the halogenation activity of heme peroxidases. Explanations are given in the text.

Figure 3
Figure 3

Major antagonizing principles controlling the halogenation activity of MPO and EPO at inflammatory sites. Explanations are given in the text.

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References

    1. Zámocký M., Jakopitsch C., Furtmüller P.G., Dunand C., Obinger C. The peroxidase-cyclooxygenase superfamily: Reconstructed evolution of critical enzymes of the innate immune system. Proteins. 2008;72:589–605. doi: 10.1002/prot.21950. - DOI - PubMed
    1. Zámocký M., Hofbauer S., Schaffner I., Gasselhuber B., Nicolussi A., Soudi M., Pirker K.F., Furtmüller P.G., Obinger C. Independent evolution of four heme peroxidase superfamilies. Arch. Biochem. Biophys. 2015;574:108–119. doi: 10.1016/j.abb.2014.12.025. - DOI - PMC - PubMed
    1. Arnhold J., Flemmig J. Human myeloperoxidase in innate and acquired immunity. Arch. Biochem. Biophys. 2010;500:92–106. doi: 10.1016/j.abb.2010.04.008. - DOI - PubMed
    1. Rothenberg M.E., Hogan S.P. The eosinophil. Annu. Rev. Immunol. 2006;24:147–174. doi: 10.1146/annurev.immunol.24.021605.090720. - DOI - PubMed
    1. Flemmig J., Gau J., Schlorke D., Arnhold J. Lactoperoxidase as a potential drug target. Expert Opin. Ther. Targets. 2016;20:447–461. doi: 10.1517/14728222.2016.1112378. - DOI - PubMed

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