The reaction between nitrite and deoxyhemoglobin. Reassessment of reaction kinetics and stoichiometry. J Biol Chem 2005 Sep 02;280(35):31126-31
Date
04/20/2005Pubmed ID
15837788DOI
10.1074/jbc.M501496200Scopus ID
2-s2.0-23644459872 (requires institutional sign-in at Scopus site) 239 CitationsAbstract
Recent evidence suggests that the reaction between nitrite and deoxygenated hemoglobin provides a mechanism by which nitric oxide is synthesized in vivo. This reaction has been previously defined to follow second order kinetics, although variable product stoichiometry has been reported. In this study we have re-examined this reaction and found that under fully deoxygenated conditions the product stoichiometry is 1:1 (methemoglobin:nitrosylhemoglobin), and unexpectedly, the kinetics deviate substantially from a simple second order reaction and exhibit a sigmoidal profile. The kinetics of this reaction are consistent with an increase in reaction rate elicited by heme oxidation and iron-nitrosylation. In addition, conditions that favor the "R" conformation show an increased rate over conditions that favor the "T" conformation. The reactivity of nitrite with heme is clearly more complex than has been previously realized and is dependent upon the conformational state of the hemoglobin tetramer, suggesting that the nitrite reductase activity of hemoglobin is under allosteric control.
Author List
Huang KT, Keszler A, Patel N, Patel RP, Gladwin MT, Kim-Shapiro DB, Hogg NAuthors
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinAgnes Keszler PhD Research Scientist I in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Allosteric RegulationElectron Spin Resonance Spectroscopy
Hemoglobins
Humans
Models, Biological
Nitrites
Oxidation-Reduction
Oxygen
Protein Conformation
