Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1)

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 is an enzyme essential for the biosynthesis of the universal sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) from ATP and inorganic sulfate. PAPS is required for all cellular sulfation reactions, which are key in the metabolism of endogenous compounds (such as steroids and glycosaminoglycans) and xenobiotics, including drugs. In humans, PAPSS1 carries out two sequential enzymatic activities: ATP sulfurylase and APS kinase. Defects in this enzyme are associated with certain skeletal dysplasias and may influence drug response, notably via pathways affecting estrogen receptor regulation in cancer. There are two PAPS synthase isoforms in humans (PAPSS1 and PAPSS2), each with distinct functional and stability profiles. No widely used targeted therapies exist for PAPSS1, but its essential role in drug metabolism underscores therapeutic relevance as a metabolic regulator.[1][3][4][7][9][10]

Other names

PAPS synthase 1PAPSS 1ATPSK1SK 1SK1PAPSSSulfurylase[8]

Drugs affecting sulfotransferase activity or metabolism depend on adequate PAPS generation by PAPSS1 for sulfate conjugation and detoxification[5]. Modulation of estrogen receptor activity observed as an indirect effect in ovarian cancer cells[10].