Cystathionine beta-synthase

Cystathionine beta-synthase (CBS) is a hydro-lyase that catalyzes the first committed step of the transsulfuration pathway, converting L-homocysteine and L-serine to L-cystathionine, the precursor of L-cysteine (UniProt: P35520). The enzyme also participates in hydrogen sulfide production, a gasotransmitter with neuroprotective signaling functions. CBS deficiency causes homocystinuria with diverse clinical manifestations including intellectual disability, skeletal abnormalities, and thromboembolism (UniProt: P35520).

CBS is relevant to Alzheimer's disease pathology. In human post-mortem AD brain tissue compared to age-matched controls, CBS was significantly upregulated with a mean log2 fold-change of 0.77 across analyzed subcellular fractions (Chaparral AD proteomics). This upregulation suggests increased transsulfuration pathway activity and potentially enhanced hydrogen sulfide production in AD brain, consistent with a putative compensatory or protective response to oxidative stress and neurodegeneration characteristic of the disease.