The role of thiotaurine in hydrogen sulfide metabolism: production, storage, therapeutic potential.

Reactive sulfur species (RSS) produced by oxidation of hydrogen sulfide (H2S) are collectively named sulfane sulfur-containing molecules. Sulfane sulfur is a highly reactive sulfur form with the unique ability to attach reversibly to other sulfur atoms. Due to its capacity to react with protein thiols to generates persulfides, sulfane sulfur plays regulatory roles in biological systems. The transsulfuration pathway is the main source of sulfane sulfur-containing compounds. However, beyond transsulfuration path, H2S oxidation pathways can generate a series of RSS involved in various pathophysiological processes. Interestingly, thiotaurine is a cysteine-derived metabolite bearing a reactive sulfane sulfur. Thiotaurine is produced metabolically by transsulfuration and it has been investigated for its role in modulating inflammation by influencing human neutrophil functional responses. As a result, thiotaurine with its peculiar sulfane sulfur moiety, can play a role in H₂S-mediated cell signaling mechanisms. In this study, the generation of thiotaurine from hypotaurine and H₂S by horseradish peroxidase was observed. Heme-dependent sulfide oxidation pathways were revealed to be significant sources of RSS. Furthermore, the formation of hypotaurine and the release of H₂S from thiotaurine were investigated using ascorbate and glutathione. Finally, we propose thiotaurine as a safe, non-toxic storage form of H2S and a key intermediate in the biochemical routes of transport, storage and release of sulfide. Given these properties, thiotaurine could be considered as H2S/sulfane sulfur donor with potential therapeutical application. The health benefits of sulfur-based therapy, such as sulfur water springs, garlic, and cruciferous vegetables, has been recognized since ancient times. Notably, the common denominator in these remedies lies in their ability to supply H2S/sulfane sulfur, further supporting the therapeutic potential of sulfane sulfur compounds, such as thiotaurine.