Cystathionine gamma-lyase, Cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase (CSE, CBS, 3-MST)

The term "hydrogen sulfide pathway enzymes" refers collectively to three main mammalian enzymes responsible for the endogenous biosynthesis of hydrogen sulfide (H₂S) from amino acid substrates. These are cystathionine gamma‐lyase (CSE), cystathionine beta‐synthase (CBS), and 3‐mercaptopyruvate sulfurtransferase (3‐MST). Each enzyme catalyzes distinct steps within the transsulfuration or cysteine catabolic pathways using methionine-derived intermediates such as homocysteine and cysteine as substrates. These enzymatic activities regulate cellular levels of H₂S—a gaseous signaling molecule ("gasotransmitter") involved in diverse biological processes including vasodilation via potassium channel activation, neuromodulation, cytoprotection against oxidative stress by boosting glutathione synthesis/reducing ROS levels,[1] regulation of apoptosis/inflammation,[4] cell proliferation/differentiation,[2] mitochondrial bioenergetics,[3] and cross-talk with nitric oxide signaling.[7] Dysregulation has been implicated in cardiovascular diseases such as hypertension and atherosclerosis,[8] neurodegeneration, cancer biology,[1] diabetes/metabolic syndrome,[5] among others. While no approved drugs specifically target these human enzymes clinically yet, experimental inhibitors/modulators exist that alter their activity for research into potential therapies.

Other names

H2S-producing enzymesH2S synthasesTranssulfuration pathway enzymes

Inhibition or activation of enzymatic activity alters endogenous hydrogen sulfide levels. Modulation affects downstream signaling pathways such as vasodilation via KATP channel activation or anti-inflammatory effects through redox modulation.[7]