Bifunctional purine biosynthesis protein ATIC

ATIC (Bifunctional purine biosynthesis protein ATIC) is a 592-amino-acid enzyme catalyzing the final two steps of purine biosynthesis (UniProt: P31939). It functions as a transformylase and cyclase, converting AICAR to FAICAR and then to IMP, using either 10-formyldihydrofolate or 10-formyltetrahydrofolate as a formyl donor. The enzyme also processes thio-AICAR to 6-mercaptopurine ribonucleotide, a chemotherapeutic agent, and independently promotes insulin receptor autophosphorylation and internalization.

ATIC deficiency causes AICA-ribosuria, a severe autosomal recessive inborn error of purine metabolism characterized by neurological devastation, intellectual disability, epilepsy, and congenital blindness (UniProt: P31939, MIM 608688). The protein is central to purine biosynthesis and nucleotide metabolism pathways essential for neuronal function.

ATIC shows ambiguous regulation in Alzheimer's Disease, with a mean log2 fold-change of −0.0195 across three subcellular fractions from TMT-labeled post-mortem AD brain versus age-matched controls (Chaparral AD proteomics). This minimal change suggests no clear directional dysregulation in AD, though subcellular redistribution across the four fractions examined may warrant further investigation.