Enzymology of H2S biogenesis, decay and signaling

Antioxid Redox Signal. 2014 Feb 10;20(5):770-82. doi: 10.1089/ars.2013.5339. Epub 2013 Jun 7.


Significance: Hydrogen sulfide (H2S), produced by the desulfuration of cysteine or homocysteine, functions as a signaling molecule in an array of physiological processes including regulation of vascular tone, the cellular stress response, apoptosis, and inflammation.

Recent advances: The low steady-state levels of H2S in mammalian cells have been recently shown to reflect a balance between its synthesis and its clearance. The subversion of enzymes in the cytoplasmic trans-sulfuration pathway for producing H2S from cysteine and/or homocysteine versus producing cysteine from homocysteine, presents an interesting regulatory problem.

Critical issues: It is not known under what conditions the enzymes operate in the canonical trans-sulfuration pathway and how their specificity is switched to catalyze the alternative H2S-producing reactions. Similarly, it is not known if and whether the mitochondrial enzymes, which oxidize sulfide and persulfide (or sulfane sulfur), are regulated to increase or decrease H2S or sulfane-sulfur pools.

Future directions: In this review, we focus on the enzymology of H2S homeostasis and discuss H2S-based signaling via persulfidation and thionitrous acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Catalytic Domain
  • Cystathionine beta-Synthase / chemistry
  • Cystathionine beta-Synthase / metabolism*
  • Cystathionine gamma-Lyase / chemistry
  • Cystathionine gamma-Lyase / metabolism*
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Mitochondrial Proteins / metabolism
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Oxidation-Reduction
  • Signal Transduction*
  • Sulfides / metabolism
  • Sulfurtransferases / chemistry
  • Sulfurtransferases / metabolism*


  • ETHE1 protein, human
  • Mitochondrial Proteins
  • Nucleocytoplasmic Transport Proteins
  • Sulfides
  • persulfides
  • Sulfurtransferases
  • 3-mercaptopyruvate sulphurtransferase
  • Cystathionine beta-Synthase
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide