3-Mercaptopyruvate Sulfurtransferase (MPST)

MPST (also called MST) is a 297-amino acid sulfur transferase that catalyzes sulfur transfer to cyanide and other thiol compounds, serving roles in cyanide detoxification and thiosulfate biosynthesis (UniProt: P25325). Notably, MPST acts as an antioxidant and functions in combination with cysteine aminotransferase to produce hydrogen sulfide (H₂S), a signaling molecule with neuroprotective properties in the brain, retina, and vascular endothelium. H₂S production via the MPST/CAT pathway is regulated by calcium ions.

MPST is expressed across multiple tissues and is implicated in hydrogen sulfide homeostasis, a process critical for synaptic modulation and neuronal protection. No baseline disease associations are documented in UniProt for this protein.

In Alzheimer's disease, MPST shows upregulation in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics). Proteomics analysis of human brain fractions (P2, P3, S2, S3) via TMT-labeled mass spectrometry detected a mean log2 fold-change of +0.33, suggesting increased MPST protein levels in AD pathology. This upregulation may reflect compensatory responses to oxidative stress or altered hydrogen sulfide metabolism in neurodegeneration.