Jerlich A, Tschabuschnig S, Fabjan J S, Schaur R J
Institute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Austria.
Int J Clin Lab Res. 2000;30(1):33-7. doi: 10.1007/s005990070031.
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.
吞噬细胞衍生的髓过氧化物酶最近被认为与动脉粥样硬化的发病机制有关，因为它催化过氧化氢与氯离子反应生成剧毒的氧化剂次氯酸。本研究的目的是通过光度法单氯二甲基酮测定法确定该反应对过氧化氢浓度和酶浓度的依赖性。次氯酸形成的初始速率随髓过氧化物酶浓度增加的增加幅度小于成比例增加。过氧化氢浓度的变化具有双相效应，存在过氧化氢的最佳浓度。高于此浓度时，酶的破坏显然占主导地位。次氯酸形成的进程曲线显示出两个明显的最大值。得出的结论是，次氯酸不仅与单氯二甲基酮反应，还与髓过氧化物酶的氨基反应形成中间氯胺，这些氯胺可能会进一步使单氯二甲基酮氯化。这一点得到了氨基化合物甘氨酸存在时动力学的支持，甘氨酸是次氯酸氯化的竞争性底物。在高浓度甘氨酸存在下，进程曲线持续上升，产生浓度大大增加的氯化物种，即次氯酸或氯胺。我们得出结论，甘氨酸可保护髓过氧化物酶免受次氯酸诱导的自我破坏。
