The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem 2008 Apr 11;283(15):9615-22
Date
01/22/2008Pubmed ID
18203719Pubmed Central ID
PMC2442280DOI
10.1074/jbc.M705630200Scopus ID
2-s2.0-44349096391 (requires institutional sign-in at Scopus site) 117 CitationsAbstract
The nitrite anion (NO(-)(2)) has recently received much attention as an endogenous nitric oxide source that has the potential to be supplemented for therapeutic benefit. One major mechanism of nitrite reduction is the direct reaction between this anion and the ferrous heme group of deoxygenated hemoglobin. However, the reaction of nitrite with oxyhemoglobin (oxyHb) is well established and generates nitrate and methemoglobin (metHb). Several mechanisms have been proposed that involve the intermediacy of protein-free radicals, ferryl heme, nitrogen dioxide (NO(2)), and hydrogen peroxide (H(2)O(2)) in an autocatalytic free radical chain reaction, which could potentially limit the usefulness of nitrite therapy. In this study we show that none of the previously published mechanisms is sufficient to fully explain the kinetics of the reaction of nitrite with oxyHb. Based on experimental data and kinetic simulation, we have modified previous models for this reaction mechanism and show that the new model proposed here is consistent with experimental data. The important feature of this model is that, whereas previously both H(2)O(2) and NO(2) were thought to be integral to both the initiation and propagation steps, H(2)O(2) now only plays a role as an initiator species, and NO(2) only plays a role as an autocatalytic propagatory species. The consequences of uncoupling the roles of H(2)O(2) and NO(2) in the reaction mechanism for the in vivo reactivity of nitrite are discussed.
Author List
Keszler A, Piknova B, Schechter AN, Hogg NAuthors
Neil Hogg PhD Senior Associate Dean, Professor in the Biophysics department at Medical College of WisconsinAgnes Keszler Research Scientist I in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnionsFree Radicals
Heme
Humans
Hydrogen Peroxide
Kinetics
Methemoglobin
Models, Chemical
Nitrates
Nitrites
Oxidation-Reduction
Oxyhemoglobins
