The quaternary hemoglobin conformation regulates the formation of the nitrite-induced bioactive intermediate and the dissociation of nitric oxide from this intermediate

Joseph M. Rifkind, Enika Nagababu, Somasundaram Ramasamy

Research output: Contribution to journalArticle

Abstract

Deoxyhemoglobin reduces nitrite to nitric oxide (NO). In order to study the effect of the hemoglobin quaternary conformation on the nitrite reaction, we compared T-state deoxyhemoglobin with R-state deoxyhemoglobin produced by reacting hemoglobin with carboxypeptidase-A prior to deoxygenation. The nitrite reaction with deoxyhemoglobin was followed by chemiluminescence, electron paramagnetic resonance and visible spectroscopy. The initial steps in this reaction involve the binding of nitrite to deoxyhemoglobin followed by the formation of an electron delocalized metastable intermediate that retains potential NO bioactivity. This reaction is shown by visible spectroscopy to occur 5.6 times faster in the R-state than in the T-state. However, the dissociation of NO from the delocalized intermediate is shown to be facilitated by the T-quaternary conformation with a 9.6 fold increase in the rate constant. The preferred NO-release in the T-state, which has a higher affinity for the membrane, can result in the NO diffusing out of the RBC and being released to the vasculature at low partial pressures of oxygen.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalNitric Oxide - Biology and Chemistry
Volume24
Issue number2
DOIs
StatePublished - Mar 15 2011

Keywords

  • Hemoglobin quaternary conformation
  • Nitric oxide
  • Nitrite reduction

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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