Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control

Abstract

The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase substrates. Human peroxidases can be divided into two groups: (1) True peroxidases are enzymes whose main function is to generate free radicals in the peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The major true peroxidases are myeloperoxidase, eosinophil peroxidase and lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in the body, but under the influence of external conditions they can display peroxidase-like activity. As oxidative intermediates, these peroxidases produce not only active heme compounds, but also protein-based tyrosyl radicals. Hemoglobin, myoglobin, cytochrome c/cardiolipin complexes and cytoglobin are considered as pseudo-peroxidases. Рeroxidases play an important role in innate immunity and in a number of physiologically important processes like apoptosis and cell signaling. Unfavorable excessive peroxidase activity is implicated in oxidative damage of cells and tissues, thereby initiating the variety of human diseases. Hence, regulation of peroxidase activity is of considerable importance. Since peroxidases differ in structure, properties and location, the mechanisms controlling peroxidase activity and the biological effects of peroxidase products are specific for each hemoprotein. This review summarizes the knowledge about the properties, activities, regulations and biological effects of true and pseudo-peroxidases in order to better understand the mechanisms underlying beneficial and adverse effects of this class of enzymes.

Evidences for a nutritional role of iodine in plants

“…They are abundant in root tissues, in which high concentrations of H2O2 occur during root development (Dunand, Crèvecoeur & Penel, 2007). In the presence of low concentrations of iodide, various peroxidases catalytically degrade H2O2 at neutral pH values, generating hypoiodous acid (HIO) (Davies, Hawkins, Pattison & Rees, 2008;Vlasova, 2018), a strong iodinating agent that can modify proteins in the environment surrounding the site of its generation, also inducing modification at Tyr. Our findings thus suggest that the class III peroxidases involved in the neutralization of H2O2 present in root tissues, in the presence of iodide and resulting HIO, become themselves the targets of iodination, which in our study occurred at different Tyr residues in their structure.…”

Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of Cytochromecand Cardiolipin

“…Jeckyll and Mr. Hyde). Heme peroxidases constitute a vital and ubiquitous group of heme enzymes catalyzing the twoelectron oxidation of substrates using H 2 O 2 as the ultimate electron acceptor [147,148]. In canonical peroxidases, H 2 O 2 is added to the pentacoordinated, high-spin Fe III .…”

“…The orientation of these residues and the hydrogen-bond network at the heme distal side are critical for efficient formation of Compound I [154]. As recently pointed out by Vlasova [148], the composition of a true peroxidase active site prevents its damage by highly oxidizing intermediate compounds.…”

“…Cc and other hemeproteins can act as pseudoperoxidases; that is, under only certain stimuli they show peroxidase activity [148,155]. Contrary to true peroxidases, the surroundings of heme moiety are unprotected against oxidation, so the peroxidase activity ends up damaging the protein.…”

“…Unlike true peroxidases, the environment of the heme moiety is unprotected from highly oxidizing species arising during the catalytic cycle [148]. When reacting with H 2 O 2 , degradation of the heme porphyrin often becomes apparent by a diminution of the Soret band intensity [146,156].…”