Hydrogen sulfide signaling system (H2S signaling)

The hydrogen sulfide (H2S) signaling system is a critical gasotransmitter network involved in a wide array of physiological and pathological processes [1.1.2, 1.2.1]. Endogenous H2S is primarily synthesized by three enzymes: cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) [1.1.3, 1.3.1]. It functions as a signaling molecule through the post-translational modification of protein cysteine residues, a process termed S-sulfhydration or persulfidation, which alters the function of targets such as K_ATP channels, transcription factors like Nrf2 and NF-kB, and various enzymes [1.1.2, 1.4.2]. This system is essential for cardiovascular homeostasis, neuronal modulation, and the regulation of inflammatory and oxidative stress responses [1.2.2, 1.3.3]. Dysregulation of H2S levels is linked to diseases such as hypertension, atherosclerosis, Alzheimer's disease, and certain cancers [1.2.1, 1.2.5]. Pharmacological interventions focus on H2S donors for supplementation or enzyme inhibitors to reduce excessive production, although the narrow therapeutic range and the inherent toxicity of H2S at high concentrations present significant clinical challenges [1.3.1, 1.4.1].

Other names

H2S signaling pathwayGasotransmitter signaling systemHydrogen sulfide biogenesis and signaling

H2S donors release hydrogen sulfide gas, which acts via protein S-sulfhydration (persulfidation) of cysteine residues to modulate targets like K_ATP channels and transcription factors; enzyme inhibitors (e.g., PAG, AOAA) reduce endogenous H2S production.