Alternative means to elevate of suppress biologic H2S levels
| Elevating H2S Levels | Suppressing H2S Levels | |||
|---|---|---|---|---|
| Approach | Example | Approach | Example | |
| Modulating H2S degradation | Inhibiting H2S metabolizing enzymes | Rhodanese deficiency (TST−/− systems); SQR silencing and ETHE1 deficiency boost H2S levels. Antioxidants reduce ROS-mediated H2S degradation and boost H2S levels | Activating H2S metabolizing enzymes | SQR or rhodanese overexpression? No pharmacological approaches |
| Modulating semistable H2S “pools” | Administering H2S metabolites or enhancing H2S regeneration from endogenous H2S “pools” | Thiosulfate and sulfane sulfur administration can elevate H2S levels and produce biologic effects consistent with H2S generation. Aspirin has been shown to accelerate H2S release from sulfane sulfur | Inhibiting the clearance or excretion of H2S metabolites? | No known pharmacological approaches |
| Regulating the expression of H2S-producing enzymes | Upregulating CBS, CSE or 3-MST expression | Upregulation of enzyme expression (e.g. using taurine) Overexpression of H2S producing enzymes as as an experimental tool. Inhibition of CBS degradation (LON protease inhibitors) | Downregulating CBS, CSE, or 3-MST expression | Inhibiting enzyme expression? Enhancing CBS degradation by ubiquitination enhancers or protease activators? |
| Alternative ways of regulating the enzymatic production of H2S | Increasing CBS, CSE, or 3-MST-mediated H2S production | Supplementation of substrates (l-cysteine, homocysteine for CBS/CSE), 3-MP for 3-MST. Activating CBS by its cofactor SAM. Some of the H2S donors (garlic-derived polysulfides, S-propargly-cysteine) rely, in part on CSE-mediated conversion for H2S production in biologic systems | Increasing CBS-, CSE-, or 3-MST-mediated H2S production | Depleting substrates (l-cysteine, homocysteine for CBS/CSE), 3-MP for 3-MST. Administering cysteinase (cancer therapy). Inhibiting CBS by blocking its cofactor binding |