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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Catalytic generation of N
2
O
3
by the concerted nitrite reductase and anhydrase activity of hemoglobin
Nature Chemical Biology, Volume 3, No. 12, Year 2007
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Description
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 (N 2O3) 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. N 2O3 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. © 2007 Nature Publishing Group.
Authors & Co-Authors
Basu, Swati
United States, Winston Salem
Wake Forest University
Grubina, Rozalina
United States, Bethesda
National Heart, Lung, and Blood Institute Nhlbi
United States, Bethesda
National Institutes of Health Nih
Huang, Jinming
United States, Winston Salem
Wake Forest University
Conradie, Jeanet
Norway, Tromso
Uit Norges Arktiske Universitet
South Africa, Bloemfontein
University of the Free State
Huang, Zhi
United States, Bethesda
National Heart, Lung, and Blood Institute Nhlbi
Jeffers, Anne
United States, Winston Salem
Wake Forest University School of Medicine
Jiang, Alice
United States, Winston Salem
Wake Forest University
He, Xiaojun
United States, Winston Salem
Wake Forest University
Azarov, Ivan
United States, Winston Salem
Wake Forest University
Seibert, Ryan
United States, Winston Salem
Wake Forest University
Mehta, Atul
United States, Winston Salem
Wake Forest University
Patel, Rakesh P.
United States, Birmingham
The University of Alabama at Birmingham
King, Stephen Bruce
United States, Winston Salem
Wake Forest University
Hogg, Neil
United States, Milwaukee
Medical College of Wisconsin
Ghosh, Abhik
Norway, Tromso
Uit Norges Arktiske Universitet
Gladwin, Mark T.
United States, Bethesda
National Heart, Lung, and Blood Institute Nhlbi
United States, Bethesda
National Institutes of Health Nih
Kim-Shapiro, Daniel B.
United States, Winston Salem
Wake Forest University
United States, Winston Salem
Wake Forest University School of Medicine
Statistics
Citations: 201
Authors: 17
Affiliations: 8
Identifiers
Doi:
10.1038/nchembio.2007.46
e-ISSN:
15524469