Dunford H B, Hsuanyu Y
Department of Chemistry, University of Alberta, Edmonton, Canada.
Biochem Cell Biol. 1999;77(5):449-57.
The oxidation of serotonin (5-hydroxytryptamine) by the myeloperoxidase intermediates compounds I and II was investigated by using transient-state spectral and kinetic measurements at 25.0 +/- 0.1 degrees C. Rapid scan spectra demonstrated that both compound I and compound II oxidize serotonin via one-electron processes. Rate constants for these reactions were determined using both sequential-mixing and single-mixing stopped-flow techniques. The second order rate constant obtained for the one-electron reduction of compound I to compound II by serotonin is (1.7 +/- 0.1) x 10(7) M(-1) x s(-1), and that for compound II reduction to native enzyme is (1.4 +/- 0.1) x 10(6) M(-1) x s(-1) at pH 7.0. The maximum pH of the compound I reaction with serotonin occurs in the pH range 7.0-7.5. At neutral pH, the rate constant for myeloperoxidase compound I reacting with serotonin is an order of magnitude larger than for its reaction with chloride, (2.2 +/- 0.2) x 10(6) M(-1) x s(-1). A direct competition of serotonin with chloride for myeloperoxidase compound I oxidation was observed. Our results suggest that serotonin may have a role to protect lipoproteins from oxidation and to prevent enzymes from inactivation caused by the potent oxidants HOCl and active oxygen species.
在25.0±0.1℃下，通过瞬态光谱和动力学测量研究了髓过氧化物酶中间体化合物I和化合物II对血清素（5-羟色胺）的氧化作用。快速扫描光谱表明，化合物I和化合物II均通过单电子过程氧化血清素。使用顺序混合和单混合停流技术测定了这些反应的速率常数。血清素将化合物I单电子还原为化合物II的二级速率常数为(1.7±0.1)×10⁷ M⁻¹×s⁻¹，在pH 7.0时，化合物II还原为天然酶的二级速率常数为(1.4±0.1)×10⁶ M⁻¹×s⁻¹。化合物I与血清素反应的最大pH值出现在7.0 - 7.5的pH范围内。在中性pH下，髓过氧化物酶化合物I与血清素反应的速率常数比其与氯离子反应的速率常数大一个数量级，即(2.2±0.2)×10⁶ M⁻¹×s⁻¹。观察到血清素与氯离子对髓过氧化物酶化合物I氧化存在直接竞争。我们的结果表明，血清素可能在保护脂蛋白免受氧化以及防止酶因强氧化剂次氯酸和活性氧物种而失活方面发挥作用。
