髓过氧化物酶催化氨基比林氧化的机制。

The mechanism of myeloperoxidase-catalysed oxidation of aminopyrine.

Sayo H, Saito M

Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Kobe, Japan.

Xenobiotica. 1990 Sep;20(9):957-65. doi: 10.3109/00498259009046911.

Abstract

Myeloperoxidase catalysed the H2O2-supported oxidation of aminopyrine in the presence of Cl-, generating the aminopyrine cation radical (AP+.). The rate of AP+. formation was determined by monitoring the absorbance at 565 nm. The pH optimum of the reaction was around 5.0. The rate of AP+. formation increased with increasing concentration of aminopyrine. Inhibition by excess H2O2 was seen at pH 4.5-5.5. 2. When Cl- was replaced by Br-, the rate of AP+. formation increased significantly, and inhibition by H2O2 became less evident and was observed only at pH 5.5. The rate of chemical oxidation of aminopyrine by HOCl was much slower than that by Br2. 3. Compared with the chlorination of monochlorodimedone (MCD), the reaction between aminopyrine and HOCl, produced by the enzymic peroxidation of Cl-, is rate-limiting in the myeloperoxidase-catalysed oxidation of aminopyrine. The differences in kinetic behaviour between the myeloperoxidase-catalysed chlorination of MCD and oxidation of aminopyrine are explained by the low reactivity of HOCl towards aminopyrine.

摘要

在氯离子存在的情况下，髓过氧化物酶催化过氧化氢支持的氨基比林氧化反应，生成氨基比林阳离子自由基（AP+·）。通过监测565nm处的吸光度来测定AP+·的形成速率。该反应的最适pH约为5.0。AP+·的形成速率随氨基比林浓度的增加而增加。在pH 4.5 - 5.5时可观察到过量过氧化氢的抑制作用。2. 当用溴离子取代氯离子时，AP+·的形成速率显著增加，并且过氧化氢的抑制作用变得不那么明显，仅在pH 5.5时观察到。次氯酸对氨基比林的化学氧化速率比溴慢得多。3. 与一氯二甲基酮（MCD）的氯化反应相比，氯离子的酶促过氧化反应产生的次氯酸与氨基比林之间的反应，在髓过氧化物酶催化的氨基比林氧化反应中是限速反应。髓过氧化物酶催化的MCD氯化反应和氨基比林氧化反应在动力学行为上的差异，是由于次氯酸对氨基比林的反应活性较低所致。