The Intersection of NO and H2S: Persulfides Generate NO from Nitrite through Polysulfide Formation

Hydrogen sulfide (H2S) and nitric oxide (NO) are important biosignaling molecules, and their biochemistries are increasingly recognized to be intertwined. Persulfides are an oxidized product of biological H2S and have emerged as important species involved in the biological action of reactive sulfur species. Using isolated persulfides, we employed a combination of experimental and computational methods to investigate the contribution of persulfides to H2S/NO crosstalk. Our studies demonstrate that isolated persulfides react with nitrite to produce NO via polysulfide and perthionitrite intermediates. These results highlight the importance of persulfides, polysulfides, and perthionitrite as intertwined reactive nitrogen and sulfur species.