Reevaluation of the rate constants for the reaction of hypochlorous acid (HOCl) with cysteine,methionine, and peptide derivatives using a new competition kinetic approach |
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| Institution: | 1. The Heart Research Institute, Newtown, NSW 2042, Australia;2. Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia;1. Institute of Experimental Medicine of the N-W Branch of the Russian Academy of Medical Sciences, Saint-Petersburg, Russia;2. Research Institute of Physico-Chemical Medicine, Moscow, Russia;3. Saint-Petersburg State University, Saint-Petersburg, Russia;4. Belarusian State University, Minsk, Belarus;1. Institute of Biology, University of Hohenheim, Garbenstr. 30, 70599, Stuttgart, Germany;2. Institute of Animal Science, Behavioral Physiology of Livestock, University of Hohenheim, Garbenstr. 30, 70599, Stuttgart, Germany;3. HoLMiR-Hohenheim Center for Livestock Microbiome Research, University of Hohenheim, 70593, Stuttgart, Germany;1. Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China;2. Research Institute of Applied Chemistry, Shanxi University, Taiyuan 030006, China;1. Beijing Engineering Research Center of Process Pollution Control, Division of Environment Technology and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China;2. University of Chinese Academy of Sciences, Beijing, 100049, China;3. School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, United States;1. State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, 999077 Hong Kong, China;2. Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA;3. Molecular and Cellular Biology Program, University of Massachusetts, Amherst, MA 01003, USA;4. Department of Medicine and Department of Health Research and Policy, Stanford University, Stanford, CA 94305, USA |
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| Abstract: | Activated white cells use oxidants generated by the heme enzyme myeloperoxidase to kill invading pathogens. This enzyme utilizes H2O2 and Cl?, Br?, or SCN? to generate the oxidants HOCl, HOBr, and HOSCN, respectively. Whereas controlled production of these species is vital in maintaining good health, their uncontrolled or inappropriate formation (as occurs at sites of inflammation) can cause host tissue damage that has been associated with multiple inflammatory pathologies including cardiovascular diseases and cancer. Previous studies have reported that sulfur-containing species are major targets for HOCl but as the reactions are fast the only physiologically relevant kinetic data available have been extrapolated from data measured at high pH (>10). In this study these values have been determined at pH 7.4 using a newly developed competition kinetic approach that employs a fluorescently tagged methionine derivative as the competitive substrate (k(HOCl + Fmoc-Met), 1.5×108 M?1 s?1). This assay was validated using the known k(HOCl + NADH) value and has allowed revised k values for the reactions of HOCl with Cys, N-acetylcysteine, and glutathione to be determined as 3.6×108, 2.9×107, and 1.24×108 M?1 s?1, respectively. Similar experiments with methionine derivatives yielded k values of 3.4×107 M?1 s?1 for Met and 1.7×108 M?1 s?1 for N-acetylmethionine. The k values determined here for the reaction of HOCl with thiols are up to 10-fold higher than those previously determined and further emphasize the critical importance of reactions of HOCl with thiol targets in biological systems. |
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| Keywords: | Hypochlorous acid Thiols Kinetics Myeloperoxidase Glutathione Methionine Free radicals |
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