Myeloperoxidase reaction with

There is some evidence suggesting that camosine can upregulate immune function. Camosine s ability to react with hypochlorite anions (Formazyuk et al, 1992 Quinn et al, 1992) generated in activated leukocytes via the myeloperoxidase reaction, suggests that the dipeptide may limit hypochlori te-med ia ted oxidation in vivo (Pattison and Davies, 2006)... 

The fates of the G(-H) radicals in DNA are mostly determined by reactions with other substrates. Here, we consider the reactions of the G(-H) radicals with types of free radicals that are generated in vivo under conditions of oxidative stress. One of these radicals is the nitrogen dioxide radical, NO2. This radical can be generated in vivo by the oxidation of nitrite, N02, a process that can be mediated by myeloperoxidase [111, 112] as well as by other cellular oxidants [113, 114]. An alternative pathway of the generation of NO2 is the homolysis of peroxynitrite [102, 115] or nitrosoperoxycarbonate formed by the reaction of peroxynitrite with carbon dioxide [99-101]. The redox potential, E°( NO2/NO2")=1.04 V vs NHE [116] is less than that of guanine, E7[G(-H)7G] = 1.29 V vs NHE [8]. Pulse radiolysis [117] and laser flash photolysis [109] experiments have shown that, in agreement with these redox potentials, N02 radicals do not react with intact DNA. However, N02 radicals can oxidize 8-oxo-dG that has a lower redox potential ( 7=0.74 vs NHE [56]) than any of the normal nucleobases [109]. 

In vivo, peroxynitrite may be intercepted by various cellular agents which will keep its steady-state low (Table 2.4). Not all these interceptors, however, react with peroxynitrite to non-reactive products. For example, carbon dioxide enhances tyrosine nitration and thiyl radical formation. Myeloperoxidase also enhances tyrosine nitration, and in the reactions with GSH and albumin thiyl radicals are formed (for details see Arteel et al. 1999). 

D20. Drozdz, R., Naskalski, J. W., and Sznajd, J., Oxidation of amino acids and peptides in reaction with myeloperoxidase, chloride and hydrogen peroxide. Biochim. Biophys. Acta 957, 47-52 (1988). 

T. Odajima and I. Yamazaki, Myeloneperoxidase of the leukocyte of normal blood. 3. The reaction of ferric myeloperoxidase with superoxide anion. Biochim. Biophys. Acta. 284, 355-359 (1972). 

Another mechanism of myeloperoxidase-initiated DNA damage by neutrophils has been proposed by Henderson et al. [47]. These authors showed that the myeloperoxidase/hydrogen peroxide/chloride system catalyzed the chlorination of 2 -deoxycytidine into 5-chloro-2 -deoxycytidine. As HOC1 is unable to react with 2 -deoxycytidine in the absence of Cl-, it was concluded that in this case a genuine active intermediate was molecular chlorine formed by Reactions (2) and (3) ... 

Furthermore, it was found that stimulated human neutrophils are able to produce 5-chloro-2 -deoxycytidine and that the myeloperoxidase system generates just the same levels of 5-chlorocytosine in DNA and RNA in vitro (Reaction (4), Figure 28.3). It is possible that myeloperoxidase-generated chlorinated products may modify nuclear acids of pathogens and nuclear acids in host cells during inflammation. Hawkins et al. [48] suggested that DNA oxidation may be initiated by protein chloramines formed in the reaction of HOCl with histones in the nucleosome. 

The reaction of myeloperoxidase with H2O2 is complex and depends upon the concentration of H2O2 and the presence of other factor(s) within the microenvironment (Fig. 5.9). The Fe in native myeloperoxidase is in the Fe III (oxidised) state (MP03+, ferric myeloperoxidase), and this reacts with low (equimolar) concentrations of H2O2 to form compound 1, a short-lived inter-... 

Figure 5.9. Reactions of myeloperoxidase with H2O2 and 02 - See text for details.

This heme-dependent enzyme [EC 1.11.1.7] catalyzes the reaction of a donor with hydrogen peroxide to produce an oxidized donor and two water. See also Horseradish Peroxidase Ovoperoxidase Myeloperoxidase... 

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