| 11401469 |
Allegra M, Furtmuller PG, Regelsberger G, Turco-Liveri ML, Tesoriere L, Perretti M, Livrea MA, Obinger C: Mechanism of reaction of melatonin with human myeloperoxidase. . Biochem Biophys Res Commun. 2001 Mar 30;282(2):380-6.
Recently, it was suggested that melatonin (N-acetyl-5-methoxytryptamine) is oxidized by activated neutrophils in a reaction most probably involving myeloperoxidase (Biochem. Biophys. Res. Commun. (2000) 279, 657-662). Myeloperoxidase (MPO) is the most abundant protein of neutrophils and is involved in killing invading pathogens. To clarify if melatonin is a substrate of MPO, we investigated the oxidation of melatonin by its redox intermediates compounds I and II using transient-state spectral and kinetic measurements at 25 degrees C. Spectral and kinetic analysis revealed that both compound I and compound II oxidize melatonin via one-electron processes. The second-order rate constant measured for compound I reduction at pH 7 and pH 5 are (6.1 +/- 0.2) x 10 (6) M (-1) s (-1) and (1.0 +/- 0.08) x 10 (7) M (-1) s (-1), respectively. The rates for the one-electron reduction of compound II back to the ferric enzyme are (9.6 +/- 0.3) x 10 (2) M (-1) s (-1) (pH 7) and (2.2 +/- 0.1) x 10 (3) M (-1) s (-1) (pH 5). Thus, melatonin is a much better electron donor for compound I than for compound II. Steady-state experiments showed that the rate of oxidation of melatonin is dependent on the H (2) O (2) concentration, is not affected by superoxide dismutase, and is quickly terminated by sodium cyanide. Melatonin can markedly inhibit the chlorinating activity of MPO at both pH 7 and pH 5. The implication of these findings in the activated neutrophil is discussed. |
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