Affiliation:
1. The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia
2. Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia
Abstract
MPO (myeloperoxidase) catalyses the oxidation of chloride, bromide and thiocyanate by H2O2 to HOCl (hypochlorous acid), HOBr (hypobromous acid) and HOSCN (hypothiocyanous acid, also know as cyanosulfenic acid) respectively. Specificity constants indicate that thiocyanate, SCN−, is a major substrate for MPO. HOSCN is also a major oxidant generated by other peroxidases including salivary, gastric and eosinophil peroxidases. Whereas HOCl and HOBr are powerful oxidizing agents, HOSCN appears to be a less reactive, but more thiol-specific oxidant. Although it is established that HOSCN selectively targets thiols, absolute kinetic data for the reactions of thiols with HOSCN are absent from the literature. This study shows for the first time that the reactions of HOSCN with low-molecular-mass thiol residues occur with rate constants in the range from 7.3×103 M−1·s−1 (for N-acetyl-cysteine at pH 7.4) to 7.7×106 M−1·s−1 (for 5-thio-2-nitrobenzoic acid at pH 6.0). An inverse relationship between the rate of reaction and the pKa of the thiol group was observed. The rates of reaction of HOSCN with thiol-containing proteins were also investigated for four proteins (creatine kinase, BSA, β-lactoglobulin and β-L-crystallins). The values obtained for cysteine residues on these proteins are in the range 1×104– 7×104 M−1·s−1. These second-order rate constants indicate that HOSCN is a major mediator of thiol oxidation in biological systems exposed to peroxidase/H2O2 systems at (patho)physiological concentrations of halide and SCN− ions, and that HOSCN may play an important role in inflammation-induced oxidative damage.
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
112 articles.
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