Two‐electron reduction and one‐electron oxidation of organic hydroperoxides by human myeloperoxidase

FEBS Letters

Burner, Ursula¹  Jantschko, Walter¹  Obinger, Christian¹  Furtmüller, Paul Georg¹  Regelsberger, Günther¹ 

[1] Institute of Chemistry, University of Agricultural Sciences, Muthgasse 18, A-1190 Vienna, Austria

关键词: Myeloperoxidase;    Compound I;    Compound II;    Superoxide;    Peroxyl radical;    Stopped-flow spectroscopy;    MPO;    myeloperoxidase;    MPO-I;    compound I;    MPO-II;    compound II;    3-CPBA;    3-chloroperoxybenzoic acid;    PAA;    peroxyacetic acid;   

DOI  :  10.1016/S0014-5793(00)02143-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The reaction of native myeloperoxidase (MPO) and its redox intermediate compound I with hydrogen peroxide, ethyl hydroperoxide, peroxyacetic acid, t-butyl hydroperoxide, 3-chloroperoxybenzoic acid and cumene hydroperoxide was studied by multi-mixing stopped-flow techniques. Hydroperoxides are decomposed by MPO by two mechanisms. Firstly, the hydroperoxide undergoes a two-electron reduction to its corresponding alcohol and heme iron is oxidized to compound I. At pH 7 and 15°C, the rate constant of the reaction between 3-chloroperoxybenzoic acid and ferric MPO was similar to that with hydrogen peroxide (1.8×10⁷ M⁻¹ s⁻¹ and 1.4×10⁷ M⁻¹ s⁻¹, respectively). With the exception of t-butyl hydroperoxide, the rates of compound I formation varied between 5.2×10⁵ M⁻¹ s⁻¹ and 2.7×10⁶ M⁻¹ s⁻¹. Secondly, compound I can abstract hydrogen from these peroxides, producing peroxyl radicals and compound II. Compound I reduction is shown to be more than two orders of magnitude slower than compound I formation. Again, with 3-chloroperoxybenzoic acid this reaction is most effective (6.6×10⁴ M⁻¹ s⁻¹ at pH 7 and 15°C). Both reactions are controlled by the same ionizable group (average pK _a of about 4.0) which has to be in its conjugated base form for reaction.

【 授权许可】

Unknown