Predicting the Possible Physiological/Biological Utility of the Hydropersulfide Functional Group Based on Its Chemistry: Similarities Between Hydropersulfides and Selenols.

Significance: Hydropersulfides (RSSH) and related polysulfide species (RSnR, n > 2, R = alkyl, H) are highly biologically prevalent with likely important physiological functions. Due to their prevalence, many labs have begun to investigate their possible roles, especially with regards to their protective, redox, and signaling properties. Recent Advances: A significant amount of work has been performed while delineating the chemical reactivity/chemical properties of hydropersulfides, and it is clear that their overall chemistry is distinct from all other biologically relevant sulfur species (e.g., thiols, disulfides, sulfenic acids, etc.). Critical Issues: One way to predict and ultimately understand the biological functions of hydropersulfides is to focus on their unique chemistry, which should provide the rationale for why this unique functionality is present. Interestingly, some of the chemical properties of RSSH are strikingly similar to those of selenols (RSeH). Therefore, it may be important to consider the known functions of selenoproteins when speculating about the possible functions of RSSH species. Future Directions: Currently, many of the inherent chemical differences between hydropersulfides and other biological sulfur species have been established. It remains to be determined, however, whether and how these differences are utilized to accomplish specific biochemical/physiological goals. A significant aspect of elucidating the biological utility of hydropersulfides will be to determine the mechanisms of regulation of their formation and/or biosynthesis, that is, based on whether it can be determined under what cellular conditions hydropersulfides are made, more meaningful speculation regarding their functions/roles can be developed.