Biosynthesis, Quantification and Genetic Diseases of the Smallest Signaling Thiol Metabolite: Hydrogen Sulfide.

Hydrogen sulfide (HS) is a gasotransmitter and the smallest signaling thiol metabolite with important roles in human health. The turnover of HS in humans is mainly governed by enzymes of sulfur amino acid metabolism and also by the microbiome. As is the case with other small signaling molecules, disease-promoting effects of HS largely depend on its concentration and compartmentalization. Genetic defects that impair the biogenesis and catabolism of HS have been described; however, a gap in knowledge remains concerning physiological steady-state concentrations of HS and their direct clinical implications. The small size and considerable reactivity of HS renders its quantification in biological samples an experimental challenge. A compilation of methods currently employed to quantify HS in biological specimens is provided in this review. Substantial discrepancy exists in the concentrations of HS determined by different techniques. Available methodologies permit end-point measurement of HS concentration, yet no definitive protocol exists for the continuous, real-time measurement of HS produced by its enzymatic sources. We present a summary of available animal models, monogenic diseases that impair HS metabolism in humans including structure-function relationships of pathogenic mutations, and discuss possible approaches to overcome current limitations of study.