Aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)

Aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) is a bifunctional enzyme that catalyzes the last two steps of de novo purine biosynthesis, namely the transformylation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) to FAICAR and the subsequent cycling to IMP (inosine monophosphate)[1][3][5]. ATIC thus plays a central role in nucleotide synthesis, essential for DNA and RNA production, and is involved in cellular proliferation and metabolism. It requires folate derivatives as cofactors, and its activity can be selectively inhibited by certain antifolate drugs. ATIC is a validated therapeutic target, particularly in cancer chemotherapy, and mutations in its gene can lead to rare but serious inborn errors of metabolism[1][5][6].

Other names

5-Aminoimidazole-4-carboxamide ribonucleotide transformylaseAICAR transformylaseAICART5-phosphoribosyl-5-amino-4-imidazolecarboxamide formyltransferaseBifunctional purine biosynthesis protein PURH10-formyltetrahydrofolate:5-phosphoribosyl-5-amino-4-imidazolecarboxamide formyltransferaseAICAR formyltransferaseAminoimidazolecarboxamide ribonucleotide transformylaseATICTransformylase

Competitive inhibition by folate analogs (e.g., sulfonyl-containing antifolates) by mimicking the transition state in the AICAR transformylase active site. Interference with folate-dependent transfer of a formyl group, blocking the last step in purine biosynthesis.