Heme proteins and nitric oxide (NO): the neglected, eloquent chemistry in NO redox signaling and regulation

Antioxid Redox Signal. 2003 Jun;5(3):307-17. doi: 10.1089/152308603322110887.


The role of nitric oxide (NO) in cellular physiology and signaling has been an important aspect in biomedical science over the last decade. As NO is a small uncharged radical, the chemistry of NO within the redox environment of the cell dictates the majority of its biological effects. The mechanisms that have received the most attention from a biological perspective involve reactions with oxygen and superoxide, despite the rich literature of metal-NO chemistry. However, NO and its related species participate in important chemistry with metalloproteins. In addition to the well known direct interactions of NO with heme proteins such as soluble guanylate cyclase and oxyhemoglobin, there is much important, but often underappreciated, chemistry between other nitrogen oxides and heme/metal proteins. Here the basic chemistry of nitrosylation and the interactions of NO and other nitrogen oxides with metal-oxo species such as found in peroxidases and monoxygenases are discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Hemeproteins / chemistry*
  • Hemeproteins / metabolism*
  • Humans
  • Hypoxia / metabolism
  • Iron Compounds / chemistry
  • Iron Compounds / metabolism
  • Ligands
  • Mitochondria / metabolism
  • Mixed Function Oxygenases
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Oxidation-Reduction
  • Oxygen / chemistry
  • Oxygen / metabolism
  • Reactive Nitrogen Species / analogs & derivatives
  • Reactive Nitrogen Species / metabolism
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism


  • Hemeproteins
  • Iron Compounds
  • Ligands
  • Reactive Nitrogen Species
  • Repressor Proteins
  • Transcription Factors
  • Nitric Oxide
  • Mixed Function Oxygenases
  • HIF1AN protein, human
  • Nitric Oxide Synthase
  • Oxygen