S-Nitrosohemoglobin: A mechanism for its formation in conjunction with nitrite reduction by deoxyhemoglobin

Enika Nagababu, Somasundaram Ramasamy, Joseph M. Rifkind

Research output: Contribution to journalArticlepeer-review

Abstract

The formation of S-nitrosohemoglobin (SNOHb) in red cells has been a major point of contention among researchers in this field. We have delineated a new mechanism for the formation of SNOHb coupled to nitrite reduction by deoxygenated hemoglobin chains at low oxygen pressures. The establishment of this mechanism required the development of a chemiluminescence assay utilizing Cu(II) and ascorbic acid to directly measure nitrosothiols without any interference from nitrite or heme-NO. The formation of SNOHb was shown to involve a dominant nitrite-reduction intermediate with electron delocalized between the heme iron and the bound NO. The possible mechanisms for the formation of SNOHb from this intermediate in the absence of oxygen are discussed including the role for an expansion of the electron delocalized intermediate to include the β-93 cysteine residue. This extended delocalization was supported by a direct reaction with unbound NO, simultaneously producing SNOHb and Hb(II)NO, when NO reacts with metHb. The SNOHb found in red cells in vivo can, thus, be explained as originating from nitrite reduction that takes place at reduced oxygen pressures.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalNitric Oxide - Biology and Chemistry
Volume15
Issue number1
DOIs
StatePublished - Aug 1 2006

Keywords

  • Hemoglobin
  • Hypoxia
  • Iron nitrosyl hemoglobin
  • Nitric oxide
  • Nitrite
  • S-Nitrosohemoglobin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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