Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase

PAICS (bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase) is a 425-amino-acid enzyme that catalyzes two sequential reactions in the de novo purine biosynthetic pathway (UniProt: P22234). The protein is essential for nucleotide synthesis and is expressed across human tissues.

Disruption of PAICS function causes phosphoribosylaminoimidazole carboxylase deficiency (PAICSD; MIM 619859), a rare autosomal recessive inborn error of purine metabolism characterized by multiple congenital anomalies and early neonatal death (UniProt: P22234). This monogenic disorder establishes the critical role of purine synthesis in development.

In Alzheimer's disease, PAICS shows modest upregulation in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.22 across subcellular fractions in a TMT-labeled proteomics study of four compartments (Chaparral AD proteomics). This directional increase suggests purine metabolism may be altered in AD pathology, though the magnitude is modest and warrants functional validation.