P36 Redox-, coordination- and solution-chemistry of sulfide in relation to some of its biological actions

Our understanding of sulfide solution-, redox- and coordination-chemistry, even in simple buffered solution systems, is still limited. The accumulating number of controversial observations in sulfide biology is most likely related to the versatile nature of its chemical properties. We critically discuss fundamental thermodynamic and kinetic features of the reactions of sulfide that determine its biological actions. Among others we will demonstrate that protein sulfhydration is governed by redox reactions and it does not occur in a direct interaction between sulfide and reduced Cys residues [1] . As an example we show our results on the efficient inactivation of the lipid phosphatase PTEN protein in solution as well as inside intact cells upon treatment with different sulfide solutions [2] . Our data indicate that inactivation of PTEN occurs via sulfhydration of its active site Cys71 and Cys124 residues. We have several lines of evidence that sulfhydration is mediated via polysulfides that are either present as contamination or form via air oxidation in sulfide solutions. Our personal perspective on blood and tissue sulfide measurements is also communicated based on proposed biomolecule-sulfide interactions [3] . The orders of magnitude differences in measured physiological sulfide levels by chemically different methods underlie the fact that there are large sulfide reserves in biological systems. We propose that the different sulfide pools are dynamically regulated in vivo , which is an essential determining factor in the regulation of endogenous-sulfide-mediated biological functions and in avoiding sulfide-related toxic events.