Kinetics of chlorination of monochlorodimedone by myeloperoxidase
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The phagocyte-derived enzyme myeloperoxidase has been recently implicated in the pathogenesis of atherosclerosis, because it catalyzes the reaction of hydrogen peroxide with chloride ions to give the highly toxic oxidant hypochlorous acid. The aim of this study was to determine the dependence of this reaction on the concentration of hydrogen peroxide and of the enzyme by means of the photometric monochlorodimedone assay. The initial rate of hypochlorous acid formation increased less than proportionally with increasing myeloperoxidase concentrations. Variation of the concentration of hydrogen peroxide had a biphasic effect, with an optimal concentration of hydrogen peroxide. Above this concentration enzyme destruction is apparently predominant. The progress curves of hypochlorous acid formation showed two distinct maxima. It was concluded that hypochlorous acid not only reacts with monochlorodimedone but also with the amino groups of myeloperoxidase to form intermediary chloramines that may further chlorinate monochlorodimedone. This was supported by the kinetics in the presence of the amino compound glycine, a competitive substrate for chlorination by hypochlorous acid. In the presence of high concentrations of glycine the progress curve rises continuously, yielding a greatly increased concentration of chlorinating species, either hypochlorous acid or chloramines. We concluded that glycine protects myeloperoxidase against hypochlorous acid-induced self-destruction.
- Harrison E, Schultz J. Studies on the chlorinating activity of myeloperoxidase J Biol Chem 1976; 251:1371.
- Thomas EL, Grisham MB, Jefferson MM. Myeloperoxidase-dependent effect of amines on functions of isolated neutrophils. J Clin Invest 1983; 72:441. CrossRef
- Weiss SJ, Klein R, Slivka A, Wei M. Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. J Clin Invest 1982; 70:598. CrossRef
- Foote CS, Goyne TE, Lehrer RI. Assessment of chlorination by human neutrophils. Nature 1983; 301:715. CrossRef
- Kalyanaraman B, Sohnle PG. Generation of free radical intermediates from foreign compounds by neutrophil derived oxidants. J Clin Invest 1985; 75: 1618. CrossRef
- Bakkenist ARJ, Boer JEG de, Plat H, Wever R. The halide complexes of myeloperoxidase and the mechanism of the halogenation reaction. Biochim Biophys Acta 1980; 613:337.
- Stelmaszynska T, Kukovetz E, Egger E, Schauer RJ. Possible involvement of myeloperoxidase in lipid peroxidation. Int J Biochem 1992; 24:121. CrossRef
- Kettle AJ, Winterbourn CC. The mechanism of myeloperoxidase-dependent chlorination of monochlorodimedone. Biochim Biophys Acta 1988; 957:185.
- Kettle AJ, Winterbourn CC. Superoxide modulates the activity of myeloperoxidase and optimizes the production of hypochlorous acid. Biochem J 1988; 252:529.
- Morris JC. The acid ionization constant of HOCl from 5 to 35°. J Phys Chem 1966; 195:133.
- Jerlich A, Fabjan JS, Tschabuschnig S, Smirnova AV, Horakova L, Hayn M, Auer H, Guttenberger H, Leis H-J, Tatzber F, Waeg G, Schaur RJ. Human low density lipoprotein as a target of hypochlorite generated by myeloperoxidase. Free Radic Biol Med 1998; 24:1139. CrossRef
- Jerlich A, Horakova L, Fabjan JS, Giessauf S, Jürgens G, Schaur RJ. Correlation of low density lipoprotein modification by myeloperoxidase with hypochlorous acid formation. Int J Clin Lab Res. In press.
- Thomas EL, Grisham MB, Jefferson MM. Preparation and characterization of chloramines. Methods Enzymol 1986; 132:569. CrossRef
- Iwamoto H, Morita T, Kobayashi T, Hasegawa E. Subunit structures of three human myeloperoxidases. J Biochem 1988; 103:688.
- Morishita K, Kubota N, Asano S, Kaziro Y, Nagata S. Molecular cloning and characterization of c-DNA for human myeloperoxidase. J Biol Chem 1987; 262:3844.
- Kinetics of chlorination of monochlorodimedone by myeloperoxidase
International Journal of Clinical and Laboratory Research
Volume 30, Issue 1 , pp 33-37
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