On the chemical biology of the nitrite/sulfide interaction

Nitric Oxide. 2015 Apr 30;46:14-24. doi: 10.1016/j.niox.2014.12.009. Epub 2014 Dec 23.


Sulfide (H2S/HS(-)) has been demonstrated to exert an astounding breadth of biological effects, some of which resemble those of nitric oxide (NO). While the chemistry, biochemistry and potential pathophysiology of the cross-talk between sulfide and NO have received considerable attention lately, a comparable assessment of the potential biological implications of an interaction between nitrite and sulfide is lacking. This is surprising inasmuch as nitrite is not only a known bioactive oxidation product of NO, but also efficiently converted to S-nitrosothiols in vivo; the latter have been shown to rapidly react with sulfide in vitro, leading to formation of S/N-hybrid species including thionitrite (SNO(-)) and nitrosopersulfide (SSNO(-)). Moreover, nitrite is used as a potent remedy against sulfide poisoning in the clinic. The chemistry of interaction between nitrite and sulfide or related bioactive metabolites including polysulfides and elemental sulfur has been extensively studied in the past, yet much of this information appears to have been forgotten. In this review, we focus on the potential chemical biology of the interaction between nitrite and sulfide or sulfane sulfur molecules, calling attention to the fundamental chemical properties and reactivities of either species and discuss their possible contribution to the biology, pharmacology and toxicology of both nitrite and sulfide.

Keywords: Hypoxia; Nitrite; Nitroxyl; SSNO(−); Sulfane sulfur; Sulfide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biochemistry
  • Humans
  • Nitric Oxide / chemistry
  • Nitric Oxide / metabolism
  • Nitrites / chemistry*
  • Nitrites / metabolism*
  • Organ Specificity
  • Sulfides / chemistry*
  • Sulfides / metabolism*


  • Nitrites
  • Sulfides
  • Nitric Oxide