Glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (GARFT and AICARFT)

Glycinamide ribonucleotide formyltransferase (GARFT) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT) are sequential, folate-dependent transferase enzymes in the de novo purine biosynthesis pathway. GARFT catalyzes the formylation of glycinamide ribonucleotide (GAR), while AICARFT catalyzes the formylation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Both activities are essential for the production of inosine monophosphate (IMP), the precursor of AMP and GMP. These enzymes are highly active in rapidly dividing cells, making them important therapeutic targets for anticancer antifolate drugs such as pemetrexed and lometrexol. Inhibition of either enzyme disrupts nucleotide synthesis, causing anti-proliferative effects, and is explored as a strategy for cancer therapy[1][2][6].

Other names

GAR transformylase (GARFT)glycinamide ribonucleotide formyltransferase (alternative for GARFT)AICAR transformylase (AICARFT)5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (alternative for AICARFT)ATIC (gene encoding bifunctional enzyme with AICARFT and IMP cyclohydrolase activities)

Folate antagonists/antifolates—competitive inhibition of catalytic sites, thereby depleting nucleotide pools Inhibition leads to anti-proliferative effects due to impaired DNA/RNA synthesis[1][2]