Kinetics of reaction of peroxynitrite with selenium- and sulfur-containing compounds: Absolute rate constants and assessment of biological significance

• Published in: Free radical biology & medicine 2015-12, Vol.89, p.1049-1056
• Main Authors: Storkey, Corin, Pattison, David I., Ignasiak, Marta T., Schiesser, Carl H., Davies, Michael J.
• Format: Article
• Language: English
• Subjects: Antioxidants; Humans; Inflammation; Kinetics; Oxidants - chemistry; Oxidants - metabolism; Peroxynitrite; Peroxynitrous Acid - chemistry; Peroxynitrous Acid - metabolism; Protein oxidation; Selenium; Selenium Compounds - chemistry; Selenium Compounds - metabolism; Selenols; Sulfur Compounds - chemistry; Sulfur Compounds - metabolism
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2015.10.424

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 5.1×105–1.9×106M−1s−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 2.5×103M−1s−1. The rate constants for diselenides and sulfides were slower with k2 0.72–1.3×103M−1s−1 and approximately 2.1×102M−1s−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. [Display omitted] •Peroxynitrous acid (ONOOH) is a major damaging oxidant formed during inflammation•ONOOH targets sulfur species, and was hypothesized to also target selenium centers.•Rate constants for ONOOH with selenols (RSeH) are 250–830 fold higher than thiols.•Selenomethionine is ~13-fold more reactive than methionine.•Selenium compounds are major targets for ONOOH at extracellular sites.