Halogenation Activity of Mammalian Heme Peroxidases

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.

The Role of Reactive Species on Innate Immunity

“…During the oxidative burst process, cells utilize O 2 and convert it to • O 2 using the mitochondrial-membrane–bound enzyme NOx [ 148 ] and after to H 2 O 2 through a family of enzymes called superoxide dismutase SOD [ 149 ]. Then, the myeloperoxidase enzyme catalyzes the reaction between H 2 O 2 and Cl − to generate HOCl [ 150 ], Figure 6 .…”

New Application of the Commercially Available Dye Celestine Blue B as a Sensitive and Selective Fluorescent “Turn-On” Probe for Endogenous Detection of HOCl and Reactive Halogenated Species

“…MPO release can occur due to phagolysosomal leakage, cell lysis, excessive secretion or neutrophil extracellular traps (NETs) formation. MPO associated with NETs is active and mediates bacterial killing in the presence of hydrogen peroxide (H 2 O 2 ) due to mainly hypochlorous acid (HOCl) formation [ 3 , 4 ]. HOCl underlies the antibacterial activity of MPO and provides an effective elimination of pathogens.…”

“…Otherwise, accomplishing the peroxidase cycle, MPO catalyzes the successive one-electron oxidation of substrates, e.g., tyrosine, urate, nitrite, ascorbate, etc. [ 4 , 5 ].…”

Thiocyanate Reduces Motor Impairment in the hMPO-A53T PD Mouse Model While Reducing MPO-Oxidation of Alpha Synuclein in Enlarged LYVE1/AQP4 Positive Periventricular Glymphatic Vessels

“…Myeloperoxidase (MPO), abundantly present in neutrophils (up to 5% of cellular proteins) and monocytes (up to 1% of cellular protein) is commonly known to generate ROS and reactive nitrogen species [ 11 ]. MPO is a component of the armamentarium of the innate immune system, present at high levels in storage vesicles in phagocytes [ 12 ]. When neutrophils and monocytes engulf microbes, MPO-containing vesicles fuse with the phagosome releasing the enzyme which reacts in the presence of hydrogen peroxide (H 2 O 2 ) with chloride ions (Cl − ) to produce the potent oxidant, hypochlorous acid (HOCl, commonly known as bleach) [ 13 , 14 ].…”

“…While MPO-generated oxidants are microbicidal and thus beneficial, these oxidants can also damage normal cells and tissues/proteins by excess production of respective halides [ 12 , 18 ]. There has been considerable evidence linking the production of HOCl with damage to host proteins, including DNA, RNA, lipids, and (lipo)proteins (reviewed in [ 19 ]).…”