Cystathionine β-synthase (CBS)

Cystathionine β-synthase (CBS) is a pyridoxal 5′-phosphate- and heme-dependent enzyme that catalyzes the condensation of serine and homocysteine to form cystathionine as the first step in the transsulfuration pathway. It plays a critical role in the regulation of homocysteine levels, acting as the main route for homocysteine detoxification in mammals. CBS is a key source of endogenous hydrogen sulfide (H₂S), a gaseous cell signaling molecule involved in vascular, neural, and immune functions. Mutations or deficiency in CBS cause homocystinuria, an inherited disorder associated with vascular and connective tissue pathology, developmental delay, and increased risk for cardiovascular and neurodegenerative diseases. CBS is also upregulated in certain cancers and Down syndrome, making it a potential therapeutic target for these conditions. Allosteric regulation of CBS occurs through S-adenosylmethionine, and its activity is modulated by cellular redox status. Direct pharmacological targeting of CBS remains challenging due to enzyme complexity and off-target risks.

Other names

CBSCystathionine beta-synthaseEC 4.2.1.22

Inhibition of CBS enzymatic activity (aminooxyacetic acid and other inhibitors). Modulation of allosteric regulation via S-adenosylmethionine binding.