The Quantitative Significance of the Transsulfuration Enzymes for H2S Production in Murine Tissues

The enzymes of the transsulfuration pathway, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), are important for the endogenous production of hydrogen sulfide (H2S), a gaseous signaling molecule. The relative contributions of CBS and CSE to H2S generation in different tissues are not known. In this study, we report quantification of CBS and CSE in murine liver and kidney and their contribution to H2S generation in these tissues and in brain at saturating substrate concentrations. We show that CBS protein levels are significantly lower than those of CSE; 60-fold and 20-fold in liver and kidney, respectively. Each enzyme is more abundant in liver compared with kidney, twofold and sixfold for CBS and CSE, respectively. At high substrate concentrations (20 mM each cysteine and homocysteine), the capacity for liver H2S production is approximately equal for CBS and CSE, whereas in kidney and brain, CBS constitutes the major source of H2S, accounting for similar to 80% and similar to 95%, respectively, of the total output. At physiologically relevant concentrations of substrate, and adjusting for the differences in CBS versus CSE levels, we estimate that CBS accounts for only 3% of H2S production by the transsulfuration pathway enzymes in liver. Antioxid. Redox Signal. 15, 363-372.