5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase (ATIC)

5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase is the formyltransferase domain of a bifunctional enzyme (coded by the ATIC gene), catalyzing the penultimate step in the de novo purine biosynthesis pathway: the transfer of a formyl group from 10-formyltetrahydrofolate to AICAR, yielding FAICAR and tetrahydrofolate. The full enzyme (commonly called ATIC or bifunctional purine biosynthesis protein PURH) catalyzes both this step and the final conversion of FAICAR to inosine monophosphate (IMP) via its cyclohydrolase activity. This enzyme is essential for rapid nucleotide production in proliferative cells, with particular relevance in oncogenesis, immune pathway activation, and metabolic regulation. It is a validated therapeutic target for antifolate drugs, especially in oncology and autoimmune disease contexts. Mutations in the ATIC gene can cause rare inborn errors of metabolism

Other names

Aminoimidazole carboxamide ribonucleotide transformylaseAICAR transformylaseAICAR formyltransferaseAICARTAICARFT5-phosphoribosyl-5-amino-4-imidazolecarboxamide formyltransferaseBifunctional purine biosynthesis protein PURHTransformylase

Inhibition by antifolates (e.g., methotrexate or methotrexate polyglutamates), resulting in blockade of de novo purine synthesis, nucleotide pool depletion, and accumulation of AICAR and related metabolites Increased extracellular adenosine due to AICAR accumulation, contributing to anti-inflammatory effects