Pg. Furtmuller et al., Two-electron reduction and one-electron oxidation of organic hydroperoxides by human myeloperoxidase, FEBS LETTER, 484(2), 2000, pp. 139-143
The reaction of native myeloperoxidase (MPO) and its redox intermediate com
pound 1 with hydrogen peroxide, ethyl hydroperoxide, peroxyacetic acid, t-b
utyl hydroperoxide, 3-chloroperoxybenzoic acid and cumene hydroperoxide was
studied by multi-mixing stopped-flow techniques, Hydroperoxides are decomp
osed by MPO by two mechanisms. Firstly, the hydroperoxide undergoes a two-e
lectron reduction to its corresponding alcohol and heme iron is oxidized to
compound I. At pH 7 and 15 degreesC, the rate constant of the reaction bet
ween 3-chloroperoxybenzoic acid and ferric MPO was similar to that with hyd
rogen peroxide (1.8x10(7) M-1 s(-1) and 1.4x10(7) M-1 s(-1), respectively).
With the exception of t-butyl hydroperoxide, the rates of compound I forma
tion varied between 5.2 x 10(5) M-1 s(-1) and 2.7 x 10(6) M-1 s(-1). Second
ly, compound I can abstract hydrogen from these peroxides, producing peroxy
l radicals and compound II. Compound I reduction is shown to be more than t
wo orders of magnitude slower than compound I formation. Again, with 3-chlo
roperoxybenzoic acid this reaction is most effective (6.6 x 10(4) M-1 s(-1)
at pH 7 and 15 degreesC). Both reactions are controlled by the same ioniza
ble group (average pK(a) of about 4.0) which has to be in its conjugated ba
se form for reaction, (C) 2000 Federation of European Biochemical Societies
, Published by Elsevier Science B.V. All rights reserved.