title: Kinetics of reaction of peroxynitrite with selenium- and sulfur-containing compounds: Absolute rate constants and assessment of biological significance.
abstract: Peroxynitrite (the physiological mixture of ONOOH and its anion, ONOO(-)) is a powerful biologically-relevant oxidant capable of oxidizing and damaging a range of important targets including sulfides, thiols, lipids, proteins, carbohydrates and nucleic acids. Excessive production of peroxynitrite is associated with several human pathologies including cardiovascular disease, ischemic-reperfusion injury, circulatory shock, inflammation and neurodegeneration. This study demonstrates that low-molecular-mass selenols (RSeH), selenides (RSeR') and to a lesser extent diselenides (RSeSeR') react with peroxynitrite with high rate constants. Low molecular mass selenols react particularly rapidly with peroxynitrite, with second order rate constants k2 in the range 5.1 × 10(5)-1.9 × 10(6)M(-1)s(-1), and 250-830 fold faster than the corresponding thiols (RSH) and many other endogenous biological targets. Reactions of peroxynitrite with selenides, including selenosugars are approximately 15-fold faster than their sulfur homologs with k2 approximately 2.5 × 10(3)M(-1)s(-1). The rate constants for diselenides and sulfides were slower with k2 0.72-1.3 × 10(3)M(-1)s(-1) and approximately 2.1 × 10(2)M(-1)s(-1) respectively. These studies demonstrate that both endogenous and exogenous selenium-containing compounds may modulate peroxynitrite-mediated damage at sites of acute and chronic inflammation, with this being of particular relevance at extracellular sites where the thiol pool is limited.
authors.affiliation: The Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Corin
authors.initials: C
authors.lastname: Storkey
authors.affiliation: The Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Pattison
authors.affiliation: Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Belgdamsvej 3, Copenhagen 2200, Denmark.
authors.forename: Marta T
authors.initials: MT
authors.lastname: Ignasiak
authors.affiliation: School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Carl H
authors.initials: CH
authors.lastname: Schiesser
authors.affiliation: The Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia; Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Belgdamsvej 3, Copenhagen 2200, Denmark. Electronic address: davies@sund.ku.dk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D006801:Humans; D007700:Kinetics; D016877:Oxidants / Q000737:chemistry* / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000737:chemistry* / Q000378:metabolism; D018036:Selenium Compounds / Q000737:chemistry* / Q000378:metabolism; D013457:Sulfur Compounds / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016877:Oxidants; D018036:Selenium Compounds; D013457:Sulfur Compounds; D030421:Peroxynitrous Acid
keywords: Antioxidants; Inflammation; Peroxynitrite; Protein oxidation; Selenium; Selenols