Small molecule signaling agents: the integrated chemistry and biochemistry of nitrogen oxides, oxides of carbon, dioxygen, hydrogen sulfide, and their derived species

Chem Res Toxicol. 2012 Apr 16;25(4):769-93. doi: 10.1021/tx2005234. Epub 2012 Feb 9.


Several small molecule species formally known primarily as toxic gases have, over the past 20 years, been shown to be endogenously generated signaling molecules. The biological signaling associated with the small molecules NO, CO, H₂S (and the nonendogenously generated O₂), and their derived species have become a topic of extreme interest. It has become increasingly clear that these small molecule signaling agents form an integrated signaling web that affects/regulates numerous physiological processes. The chemical interactions between these species and each other or biological targets is an important factor in their roles as signaling agents. Thus, a fundamental understanding of the chemistry of these molecules is essential to understanding their biological/physiological utility. This review focuses on this chemistry and attempts to establish the chemical basis for their signaling functions.

Publication types

  • Review

MeSH terms

  • Carbon Monoxide / chemistry
  • Hydrogen Sulfide / chemistry*
  • Hydrogen Sulfide / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Myoglobin / chemistry
  • Nitrogen Oxides / chemistry*
  • Nitrogen Oxides / metabolism
  • Oxygen / chemistry*
  • Reactive Nitrogen Species / chemistry
  • Reactive Oxygen Species / chemistry
  • Signal Transduction*


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Myoglobin
  • Nitrogen Oxides
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Carbon Monoxide
  • Oxygen
  • Hydrogen Sulfide