Inhibition of yeast glycolysis by nitroxyl (HNO): mechanism of HNO toxicity and implications to HNO biology

Arch Biochem Biophys. 2005 Oct 1;442(1):140-8. doi: 10.1016/


Nitroxyl (HNO) was found to inhibit glycolysis in the yeast Saccharomyces cerevisiae. The toxicity of HNO in yeast positively correlated with the dependence of yeast on glycolysis for cellular energy. HNO was found to potently inhibit the crucial glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH), an effect which is likely to be responsible for the observed inhibition of glycolysis in whole cell preparations. It is proposed that GAPDH inhibition occurs through reaction of HNO with the active site thiolate residue of GAPDH. Significantly, levels of HNO that inhibit GAPDH do not alter the levels or redox status of intracellular glutathione (GSH), indicating that HNO has thiol selectivity. The ability of HNO to inhibit GAPDH in an intracellular environment that contains relatively large concentrations of GSH is an important aspect of HNO pharmacology and possibly, physiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Catalysis
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology*
  • Glutathione / antagonists & inhibitors
  • Glutathione / metabolism
  • Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Glycolysis / drug effects*
  • Nitrogen Oxides / metabolism
  • Nitrogen Oxides / pharmacology*
  • Nitrogen Oxides / toxicity
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / metabolism
  • Time Factors


  • Enzyme Inhibitors
  • Nitrogen Oxides
  • Sulfhydryl Compounds
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Glutathione
  • nitroxyl