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Two‐electron reduction and one‐electron oxidation of organic hydroperoxides by human myeloperoxidase
Author(s) -
Furtmüller Paul Georg,
Burner Ursula,
Jantschko Walter,
Regelsberger Günther,
Obinger Christian
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02143-8
Subject(s) - chemistry , cumene hydroperoxide , hydrogen peroxide , myeloperoxidase , ferric , peroxide , reaction rate constant , photochemistry , radical , medicinal chemistry , redox , peroxidase , stereochemistry , organic chemistry , kinetics , catalysis , enzyme , medicine , physics , quantum mechanics , inflammation
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 (1.8×10 7 M −1 s −1 and 1.4×10 7 M −1 s −1 , respectively). With the exception of t ‐butyl hydroperoxide, the rates of compound I formation varied between 5.2×10 5 M −1 s −1 and 2.7×10 6 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 (6.6×10 4 M −1 s −1 at pH 7 and 15°C). Both reactions are controlled by the same ionizable group (average p K a of about 4.0) which has to be in its conjugated base form for reaction.