Metabolism of hydrogen sulfide (HS) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase.

Reactive sulfur species (RSS) such as HS, HS, HS, (n = 2-7) and HS are chemically similar to HO and the reactive oxygen species (ROS) HO, HO, O and act on common biological effectors. RSS were present in evolution long before ROS, and because both are metabolized by catalase it has been suggested that "antioxidant" enzymes originally evolved to regulate RSS and may continue to do so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved HS, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (HS-HS). HS was concentration- and oxygen-dependently oxidized by 1μM SOD to polysulfides (mainly HS, and to a lesser extent HS and HS) with an EC of approximately 380μM HS. HS concentrations > 750μM inhibited SOD oxidation (IC = 1.25mM) with complete inhibition when HS > 1.75mM. Polysulfides were not metabolized by SOD. SOD oxidation preferred dissolved HS over hydrosulfide anion (HS), whereas HS inhibited polysulfide production. In hypoxia, other possible electron donors such as nitrate, nitrite, sulfite, sulfate, thiosulfate and metabisulfite were ineffective. Manganese SOD also catalyzed HS oxidation to form polysulfides, but did not metabolize polysulfides indicating common attributes of these SODs. These experiments suggest that, unlike the well-known SOD-mediated dismutation of two O to form HO and O SOD catalyzes a reaction using HS and O to form persulfide. These can then combine in various ways to form polysulfides and sulfur oxides. It is also possible that HS (or polysulfides) interact/react with SOD cysteines to affect catalytic activity or to directly contribute to sulfide metabolism. Our studies suggest that HS metabolism by SOD may have been an ancient mechanism to detoxify sulfide or to regulate RSS and along with catalase may continue to do so in contemporary organisms.