Phosphoribosylaminoimidazolecarboxamide formyltransferase (ATIC)

Phosphoribosylaminoimidazolecarboxamide formyltransferase (ATIC) is a bifunctional enzyme that catalyzes the final two steps of de novo purine biosynthesis. Its N-terminal domain acts as an aminoimidazole carboxamide ribonucleotide transformylase ("AICAR transformylase"), transferring a one-carbon group from 10-formyltetrahydrofolate onto AICAR to produce FAICAR; its C-terminal domain functions as IMP cyclohydrolase. The enzyme plays a central role in cellular proliferation by enabling nucleotide production. It is targeted by antifolate drugs such as methotrexate for treatment of cancers and autoimmune disorders; inhibition results both in cytotoxicity toward rapidly dividing cells and increased extracellular adenosine levels with anti-inflammatory properties. Genetic variation within ATIC can influence patient responses or adverse events during therapy with these agents.

Other names

5-Aminoimidazole-4-carboxamide ribonucleotide transformylaseAICAR transformylaseAICAR formyltransferaseATICBifunctional purine biosynthesis protein PURHIMP cyclohydrolase (refers to the bifunctional nature of the protein)10-formyltetrahydrofolate:5-phosphoribosyl-5-amino-4-imidazolecarboxamide formyltransferase

Methotrexate polyglutamates inhibit ATIC, blocking conversion of AICAR to FAICAR. This leads to accumulation of AICAR and downstream adenosine, which has anti-inflammatory effects. Inhibition also disrupts purine synthesis required for DNA/RNA production in rapidly dividing cells such as cancer or immune cells.