A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells

Nat Commun. 2013;4:1366. doi: 10.1038/ncomms2371.


In eukaryotes, hydrogen sulphide acts as a signalling molecule and cytoprotectant. Hydrogen sulphide is known to be produced from L-cysteine by cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase coupled with cysteine aminotransferase. Here we report an additional biosynthetic pathway for the production of hydrogen sulphide from D-cysteine involving 3-mercaptopyruvate sulfurtransferase and D-amino acid oxidase. Unlike the L-cysteine pathway, this D-cysteine-dependent pathway operates predominantly in the cerebellum and the kidney. Our study reveals that administration of D-cysteine protects primary cultures of cerebellar neurons from oxidative stress induced by hydrogen peroxide and attenuates ischaemia-reperfusion injury in the kidney more than L-cysteine. This study presents a novel pathway of hydrogen sulphide production and provides a new therapeutic approach to deliver hydrogen sulphide to specific tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biosynthetic Pathways* / drug effects
  • Brain / drug effects
  • Brain / enzymology
  • Cells, Cultured
  • Cysteine / administration & dosage
  • Cysteine / metabolism*
  • Cysteine / pharmacology
  • Cytoprotection / drug effects
  • D-Amino-Acid Oxidase / metabolism
  • Hydrogen Sulfide / metabolism*
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Mammals / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / pathology
  • Organ Specificity / drug effects
  • Oxidative Stress / drug effects
  • Reperfusion Injury / pathology
  • Substrate Specificity / drug effects
  • Sulfurtransferases / metabolism


  • D-Amino-Acid Oxidase
  • Sulfurtransferases
  • 3-mercaptopyruvate sulphurtransferase
  • Cysteine
  • Hydrogen Sulfide