Mechanistic chemical perspective of hydrogen sulfide signaling

Methods Enzymol. 2015;554:3-29. doi: 10.1016/bs.mie.2014.11.036. Epub 2015 Jan 10.


Hydrogen sulfide is now a well-appreciated master regulator in a diverse array of physiological processes. However, as a consequence of the rapid growth of the area, sulfide biology suffers from an increasing number of controversial observations and interpretations. A better understanding of the underlying molecular pathways of sulfide's actions is key to reconcile controversial issues, which calls for rigorous chemical/biochemical investigations. Protein sulfhydration and coordination/redox chemical interactions of sulfide with heme proteins are the two most extensively studied pathways in sulfide biochemistry. These pathways are important mediators of protein functions, generate bioactive sulfide metabolites, contribute to sulfide storage/trafficking and carry antioxidant functions. In addition, inorganic polysulfides, which are oxidative sulfide metabolites, are increasingly recognized as important players in sulfide biology. This chapter provides an overview of our mechanistic perspective on the reactions that govern (i) sulfide's bioavailability (including the delicate enzyme machineries that orchestrate sulfide production and consumption and the roles of the large sulfide-storing pools as biological buffers), (ii) biological significance and mechanisms of persulfide formation (including the reduction of disulfides, condensation with sulfenic acids, oxidation of thiols with polysulfides and radical-mediated pathways), (iii) coordination and redox chemical interactions of sulfide with heme proteins (including cytochrome c oxidase, hemoglobins, myoglobins and peroxidases), and (iv) the chemistry of polysulfides.

Keywords: Antioxidant; Chemistry; Coordination; Hemeprotein; Hydrogen sulfide; Mechanism; Metalloprotein; Polysulfide; Signaling; Sulfhydration.

Publication types

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

MeSH terms

  • Animals
  • Free Radicals / metabolism
  • Hemeproteins / metabolism
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Oxidation-Reduction
  • Protein Processing, Post-Translational
  • Signal Transduction*


  • Free Radicals
  • Hemeproteins
  • Hydrogen Sulfide