Hydrogen sulfide as a gasotransmitter

Area of Science:

• Biochemistry
• Physiology
• Molecular Biology

Background:

• Nitric oxide (NO) and carbon monoxide (CO) are established gasotransmitters.
• Hydrogen sulfide (H2S) is chemically reactive, but its physiological role was unclear.
• H2S is synthesized from cyst(e)ine by cystathionine beta-synthase and cystathionine gamma-lyase (CSE).

Purpose of the Study:

• To establish the physiological significance of hydrogen sulfide (H2S) as a gasotransmitter.
• To identify the primary enzymes responsible for H2S production in different body regions.
• To elucidate the signaling mechanisms and functional impact of H2S.

Main Methods:

• Utilized genetically modified mice lacking key H2S biosynthetic enzymes (CSE and cystathionine beta-synthase).
• Assessed endothelial-derived relaxing factor activity in mesenteric arteries.
• Investigated protein modification by S-sulfhydration and compared it to S-nitrosylation.

Main Results:

• CSE is the primary enzyme for peripheral H2S production, while cystathionine beta-synthase is key in the brain.
• Deletion of CSE significantly reduced endothelial-derived relaxing factor activity, confirming H2S's role.
• H2S signals by S-sulfhydrating proteins, predominantly activating enzymes, unlike NO's inhibitory S-nitrosylation.

Conclusions:

• Hydrogen sulfide (H2S) is a major physiological gasotransmitter, comparable in importance to NO and CO.
• CSE is essential for peripheral H2S synthesis and its role as an endothelial-derived relaxing factor.
• H2S exerts its effects through S-sulfhydration, a distinct post-translational modification that activates target proteins.