Kinetics of oxidation of serotonin by myeloperoxidase compounds I and II

The oxidation of serotonin (5-hydroxytryptamine) by the myeloperoxidase int ermediates compounds I and II was investigated by using transient-state spe ctral and kinetic measurements at 25.0 +/- 0.1 C. Rapid scan spectra demons trated that both compound I and compound II oxidize serotonin via one-elect ron processes. Rate constants for these reactions were determined using bot h sequential-mixing and single-mixing stopped-flow techniques. The second o rder rate constant obtained for the one-electron reduction of compound I to compound II by serotonin is (1.7 +/- 0.1) + 10(7) M-1 s(-1), and that for compound II reduction to native enzyme is (1.4 +/- 0.1) + 10(6) M-1 s(-1) a t pH 7.0. The maximum pH of the compound I reaction with serotonin occurs i n the pH range 7.0-7.5. At neutral pH, the rate constant for myeloperoxidas e compound I reacting with serotonin is an order of magnitude larger than f or its reaction with chloride, (2.2 +/- 0.2) + 10(6) M-1 s(-1). A direct co mpetition of serotonin with chloride for myeloperoxidase compound I oxidati on was observed. Our results suggest that serotonin may have a role to prot ect lipoproteins from oxidation and to prevent enzymes from inactivation ca used by the potent oxidants HOCl and active oxygen species.