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Nitroxyl (HNO) reacts with molecular oxygen and forms peroxynitrite at physiological pH. Biological Implications. J Biol Chem 2014 Dec 19;289(51):35570-81

Date

11/08/2014

Pubmed ID

25378389

Pubmed Central ID

PMC4271240

DOI

10.1074/jbc.M114.597740

Scopus ID

2-s2.0-84919475251 (requires institutional sign-in at Scopus site)   65 Citations

Abstract

Nitroxyl (HNO), the protonated one-electron reduction product of NO, remains an enigmatic reactive nitrogen species. Its chemical reactivity and biological activity are still not completely understood. HNO donors show biological effects different from NO donors. Although HNO reactivity with molecular oxygen is described in the literature, the product of this reaction has not yet been unambiguously identified. Here we report that the decomposition of HNO donors under aerobic conditions in aqueous solutions at physiological pH leads to the formation of peroxynitrite (ONOO(-)) as a major intermediate. We have specifically detected and quantified ONOO(-) with the aid of boronate probes, e.g. coumarin-7-boronic acid or 4-boronobenzyl derivative of fluorescein methyl ester. In addition to the major phenolic products, peroxynitrite-specific minor products of oxidation of boronate probes were detected under these conditions. Using the competition kinetics method and a set of HNO scavengers, the value of the second order rate constant of the HNO reaction with oxygen (k = 1.8 × 10(4) m(-1) s(-1)) was determined. The rate constant (k = 2 × 10(4) m(-1) s(-1)) was also determined using kinetic simulations. The kinetic parameters of the reactions of HNO with selected thiols, including cysteine, dithiothreitol, N-acetylcysteine, captopril, bovine and human serum albumins, and hydrogen sulfide, are reported. Biological and cardiovascular implications of nitroxyl reactions are discussed.

Author List

Smulik R, Dębski D, Zielonka J, Michałowski B, Adamus J, Marcinek A, Kalyanaraman B, Sikora A

Authors

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Algorithms
Animals
Boron Compounds
Boronic Acids
Captopril
Cattle
Chromatography, High Pressure Liquid
Coumarins
Cysteine
Dithiothreitol
Humans
Hydrogen Sulfide
Hydrogen-Ion Concentration
Kinetics
Mass Spectrometry
Models, Chemical
Nitrogen Oxides
Oxidation-Reduction
Oxygen
Peroxynitrous Acid
Serum Albumin
Spectrophotometry
Sulfhydryl Compounds