Catalytic generation of N2O3 by the concerted nitrite reductase and anhydrase activity of hemoglobin. Nat Chem Biol 2007 Dec;3(12):785-94
Date
11/06/2007Pubmed ID
17982448DOI
10.1038/nchembio.2007.46Scopus ID
2-s2.0-36248985678 (requires institutional sign-in at Scopus site) 208 CitationsAbstract
Nitrite reacts with deoxyhemoglobin to form nitric oxide (NO) and methemoglobin. Though this reaction is experimentally associated with NO generation and vasodilation, kinetic analysis suggests that NO should not be able to escape inactivation in the erythrocyte. We have discovered that products of the nitrite-hemoglobin reaction generate dinitrogen trioxide (N2O3) via a novel reaction of NO and nitrite-bound methemoglobin. The oxygen-bound form of nitrite-methemoglobin shows a degree of ferrous nitrogen dioxide (Fe(II)-NO2*) character, so it may rapidly react with NO to form N2O3. N2O3 partitions in lipid, homolyzes to NO and readily nitrosates thiols, all of which are common pathways for NO escape from the erythrocyte. These results reveal a fundamental heme globin- and nitrite-catalyzed chemical reaction pathway to N2O3, NO and S-nitrosothiol that could form the basis of in vivo nitrite-dependent signaling. Because the reaction redox-cycles (that is, regenerates ferrous heme) and the nitrite-methemoglobin intermediate is not observable by electron paramagnetic resonance spectroscopy, this reaction has been 'invisible' to experimentalists over the last 100 years.
Author List
Basu S, Grubina R, Huang J, Conradie J, Huang Z, Jeffers A, Jiang A, He X, Azarov I, Seibert R, Mehta A, Patel R, King SB, Hogg N, Ghosh A, Gladwin MT, Kim-Shapiro DBAuthor
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
CatalysisElectron Spin Resonance Spectroscopy
Hemoglobins
Iron
Models, Molecular
Molecular Conformation
Nitrite Reductases
Nitrites
Nitrogen Oxides
Oxidation-Reduction
Oxygen
