Myeloperoxidase compounds

Winterboum, C. C., Garcia, R. C., Segal, A. W. (1985). Production of the superoxide adduct of myeloperoxidase (compound HI) by stimulated human neutrophils and its reactivity with hydrogen peroxide and chloride. Biochem. J. 228, 583-92. 

Furtmiiller PG, Burner U, Obinger C (1998) Reaction of myeloperoxidase compound I with chloride, bromide, iodide and thiocyanate. Biochemistry 37 17923-17930... 

Marquez LA, Dunford HB (1995) Kinetics of oxidation of tyrosine and dityrosine by myeloperoxidase compounds I and II. Implications for lipoprotein peroxidation studies. J Biol Chem 270 30434-30440... 

According to Reichl et al. (2000), the oxidation of pholasin by compound I or II of horseradish peroxidase induces an intense light emission, whereas native horseradish peroxidase shows only a small effect. The luminescence of pholasin by native myeloperoxidase (verdoperoxidase) is diminished by preincubation with catalase, which is interpreted as the result of the removal of a trace amount of naturally occurring H2O2 in the buffer (about 10-8 M) that forms compound I... 

These stimuli elicit a complex series of responses that result in cell functions such as chemotaxis and release of inflammatory compounds, oxidants, and proteases. Probably related to chemotaxis is a rapid, transient actin polymerization response. Inflammation results in part from the release of proteases and myeloperoxidase normally stored in granules inside the cell (5) and from oxidants produced by an NADPH-oxidase system (6) located primarily... 

The effect of gold compounds on human neutrophil myeloperoxidase, in Bioinorganic Chemistry of Gold Coordination Compounds (eds B.M. Sutton and R.G. Franz), SK F, Philadelphia, pp. 58-66. 

The plant is strongly aromatic on account of an essential oil which comprises cis-a-ocimene (25.11%), 3,7-dimethyl-l,6-octadien-3 ol (16.85%), and trans-nerolidol (13.89%), hence the use of the plant in aromatherapy. A methanolic extract of bark of Litsea cubeba (Lour.) Pers. and its fractions (0.01 mg/mL) from bark inhibit NO and PGE2 production in LPS-activated RAW 264.7 macrophages without significant cytotoxicity at less than 0.01 mg/mL concentration. The methanol extract decreased the enzymatic activity of myeloperoxidase (0.05 mg/mL). These findings suggest that L. cubeba is beneficial for inflammatory conditions and may contain compound(s) with anti-inflammatory properties (63). Can we expect the vasorelaxant laurotetanine (64) isolated from the plant to exert such activity ... 

C5a is inactivated by the myeloperoxidase-H202 system, which oxidises a methionine residue (Met 70) on the molecule group A streptococcal endo-proteinases also abolish chemotactic activity of C5a and related compounds. Neutrophil lysosomal enzymes (e.g. elastase and cathepsin G) also destroy C5a chemotactic activity, but as these proteases are inhibited by the serum antiproteinases, a -antiproteinase and a2-macroglobulin, the physiological role of neutrophilic proteases in the inactivation of C5a is questionable. Two chemotactic factor inactivators have been found in human serum an a-globulin that specifically and irreversibly inactivates C5-derived chemotactic factors, and a / -globulin that inactivates bacterial chemotactic factors. These activities are heat labile (destroyed by treatment at 56 °C for 30 min) and are distinct from those attributable to anaphylatoxin inactivator. An apparently specific inhibitor of C5-derived chemotactic activity has also been described in human synovial fluid and peritoneal fluid. This factor (molecular mass of 40 kDa) is heat stable and acts directly on C5a. 

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-... 

The transient production of compounds II and in has been reported during stimulation of neutrophils by fMet-Leu-Phe and PMA, respectively. Ferric myeloperoxidase and compound III show catalase activity, even in the presence of CP, when H2O2 concentrations are in excess of 200 pM. Thus, under these conditions, O2 formation will occur at the expense of HOCI forma-... 

Additional products of the myeloperoxidase system depend upon the local environment. For example, HOC1 can react with nitrogen-containing compounds such as biological amines to form chloramines ... 

Cuperus, R. A., Muijsers, A. O., Wever, R. (1986). The superoxide dismutase activity of myeloperoxidase formation of Compound HI. Biochim. Biophys. Acta 871, 78-84. 

The formation of cholesterol chlorohydrins has been a subject of intense research [99-102]. The role of these compounds is not yet fully understood, but in addition to cytotoxicity and a possible action on atherosclerosis [100], they have been suggested to be biomarkers of myeloperoxidase-derived HOC1 [103]. Moreover, chlorohydrins and other halohydrins are useful intermediates for the synthesis of a vast range of biologically active natural and synthetic products [104, 105], In fact, considering the importance of these compounds, their preparation is of major interest. 

The heme iron in the peroxidase is oxidized by the peroxide from III+ to V4- in compound I. The compound I is reduced by two sequential one-electron transfer processes giving rise to the original enzyme. A substrate-free radical is in turn generated. This may have toxicological implications. Thus the myeloperoxidase in the bone marrow may catalyze the metabolic activation of phenol or other metabolites of benzene. This may underlie the toxicity of benzene to the bone marrow, which causes aplastic anemia (see below and chap. 6). The myeloperoxidase found in neutrophils and monocytes may be involved in the metabolism and activation of a number of drugs such as isoniazid, clozapine, procainamide, and hydralazine (see below). In in vitro systems, the products of the activation were found to be cytotoxic in vitro. 

Subrahmanyam, V.V., Kolachana, P. Smith, M.T. (1991) Metabolism of hydroquinone by human myeloperoxidase mechamsms of stimulation by other phenolic compounds. Arch. Biochem. Biophys., 286, 76-84... 

Henderson JP, Heinecke JW (2003) Myeloperoxidase and Eosinophil Peroxidase Phagocyte Enzymes for Halogenation in Humans. In Gribble GW (ed) Natural Production of Organohalogen Compounds, The Handbook of Environmental Chemistry, vol 3, part P. Springer, Berlin, p 201... 

Pincemail J, Deby C, Thirion A, de Bruyn-Dister M, Goutier R. 1988. Fluman myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds. Cell Mol Life Sci 44 450-453. 

The direct interactions between metals and ONOO- can catalyze modifications. For example, the metals in Cu,Zn SOD and FeEDTA (EDTA = ethyl-enediaminetetraacetic acid) enhance nitration reactions (229). Heme-containing enzymes such as myeloperoxidase (6 x 106A/-1 s-1) and lactoperoxidase (3.3 x 105M-1s-1) also react with ONOO- (230) such that compound II [FeIV(P+)0] is formed. In contrast, horseradish peroxidase (3.2 x 106M-1 s-1) is converted to compound I (FevO) by ONOO-. Floris et al. (230) proposed an interesting mechanism by which compound I is initially produced and then rapidly oxidizes NO-f to N02. In the presence of NO, a number of nitrosation reactions would subsequently be facilitated by subsequent formation of N2O3 (Eq. 32). 

Amhold J, Furtmuller PG, Regelsberger G et al (2001) Redox properties of the couple compound I/native enzyme of myeloperoxidase and eosinophil peroxidase. Eur J Biochem 268 5142-5148... 

Furtmuller PG, Amhold J, Jantschko W et al (2003) Redox properties of the couples compound I/compound II and compound II/native enzyme of human myeloperoxidase. Biochem Biophys Res Commun 301 551-557... 

Another important aspect of peroxidase reactions is the relation between the substrate one-electron redox potential and the redox potential of compound I and compound II, since this restricts the number of possible redox partners (see Chap. 4 for a detailed description). Table 6.1 reports the redox potentials of some selected peroxidases as it can be seen, the values span an interval ranging from 1.35 V for reduction of myeloperoxidase (MPO) compound I to 1.0 V for reduction of HRP compound I [13-15]. But the selection of the preferred enzyme for a given radical reaction must consider not only the complementarities in the redox potentials but also the mechanism preferred by the enzyme, since some peroxidases, such as CPO and MPO, and also LPO in some cases, react through a two-electron oxidation mechanism. 

Winterboum CC (1985) Comparative reactivities of various biological compounds with myeloperoxidase-hydrogen peroxide-chloride, and similarity of the oxidant to hypochlorite. Biochim Biophys Acta 840 204—210... 

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