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

Hydrogen sulfide (H(2)S) is a gasotransmitter and the smallest signaling thiol metabolite with important roles in human health. The turnover of H(2)S 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 H(2)S largely depend on its concentration and compartmentalization. Genetic defects that impair the biogenesis and catabolism of H(2)S have been described; however, a gap in knowledge remains concerning physiological steady-state concentrations of H(2)S and their direct clinical implications. The small size and considerable reactivity of H(2)S renders its quantification in biological samples an experimental challenge. A compilation of methods currently employed to quantify H(2)S in biological specimens is provided in this review. Substantial discrepancy exists in the concentrations of H(2)S determined by different techniques. Available methodologies permit end-point measurement of H(2)S concentration, yet no definitive protocol exists for the continuous, real-time measurement of H(2)S produced by its enzymatic sources. We present a summary of available animal models, monogenic diseases that impair H(2)S metabolism in humans including structure-function relationships of pathogenic mutations, and discuss possible approaches to overcome current limitations of study.