Kettle A J, Winterbourn C C
Department of Pathology, Christchurch School of Medicine, Christchurch Hospital, New Zealand.
Biochem J. 1988 Jun 1;252(2):529-36. doi: 10.1042/bj2520529.
Myeloperoxidase catalyses the conversion of H2O2 and Cl- to hypochlorous acid (HOCl). It also reacts with O2- to form the oxy adduct (compound III). To determine how O2- affects the formation of HOCl, chlorination of monochlorodimedon by myeloperoxidase was investigated using xanthine oxidase and hypoxanthine as a source of O2- and H2O2. Myeloperoxidase was mostly converted to compound III, and H2O2 was essential for chlorination. At pH 5.4, superoxide dismutase (SOD) enhanced chlorination and prevented formation of compound III. However, at pH 7.8, SOD inhibited chlorination and promoted formation of the ferrous peroxide adduct (compound II) instead of compound III. We present spectral evidence for a direct reaction between compound III and H2O2 to form compound II, and for the reduction of compound II by O2- to regenerate native myeloperoxidase. These reactions enable compound III and compound II to participate in the chlorination reaction. Myeloperoxidase catalytically inhibited O2- -dependent reduction of Nitro Blue Tetrazolium. This inhibition is explained by myeloperoxidase undergoing a cycle of reactions with O2-, H2O2 and O2-, with compounds III and II as intermediates, i.e., by myeloperoxidase acting as a combined SOD/catalase enzyme. By preventing the accumulation of inactive compound II, O2- enhances the activity of myeloperoxidase. We propose that, under physiological conditions, this optimizes the production of HOCl and may potentiate oxidant damage by stimulated neutrophils.
髓过氧化物酶催化过氧化氢（H₂O₂）和氯离子（Cl⁻）转化为次氯酸（HOCl）。它还与超氧阴离子（O₂⁻）反应形成氧加合物（化合物III）。为了确定O₂⁻如何影响HOCl的形成，使用黄嘌呤氧化酶和次黄嘌呤作为O₂⁻和H₂O₂的来源，研究了髓过氧化物酶对一氯二甲基酮的氯化作用。髓过氧化物酶大多转化为化合物III，并且H₂O₂对于氯化是必不可少的。在pH 5.4时，超氧化物歧化酶（SOD）增强了氯化作用并阻止了化合物III的形成。然而，在pH 7.8时，SOD抑制了氯化作用并促进了过氧化亚铁加合物（化合物II）而非化合物III的形成。我们提供了光谱证据，证明化合物III与H₂O₂直接反应形成化合物II，以及O₂⁻将化合物II还原以再生天然髓过氧化物酶。这些反应使化合物III和化合物II能够参与氯化反应。髓过氧化物酶催化抑制了超氧阴离子依赖性的硝基蓝四唑还原反应。这种抑制作用可以通过髓过氧化物酶与O₂⁻, H₂O₂和O₂⁻进行反应循环来解释，其中化合物III和II作为中间体，即髓过氧化物酶起到了超氧化物歧化酶/过氧化氢酶的联合作用。通过防止无活性化合物II的积累，O₂⁻增强了髓过氧化物酶的活性。我们提出，在生理条件下，这优化了HOCl的产生，并可能通过刺激中性粒细胞增强氧化损伤作用。
