Glycinamide ribonucleotide formyltransferase (GART) (GARFT)

Glycinamide ribonucleotide formyltransferase (GARFT) is a critical enzyme in the de novo purine biosynthesis pathway, catalyzing the transfer of a formyl group from 10-formyltetrahydrofolate to glycinamide ribonucleotide (GAR) [1, 2]. In humans, this enzyme is part of a trifunctional protein encoded by the GART gene, which also possesses glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase activities [1]. Because neoplastic cells have a high demand for purines to support rapid proliferation, GARFT has emerged as a strategic target for antifolate chemotherapy [3]. Inhibitors such as lometrexol specifically target GARFT, while multi-targeted antifolates like pemetrexed inhibit GARFT alongside related folate-dependent enzymes such as thymidylate synthase and dihydrofolate reductase [3, 4]. Disruption of this enzyme leads to the depletion of intracellular purine nucleotides, resulting in the inhibition of DNA and RNA synthesis and subsequent induction of apoptosis in tumor cells [2, 5]. Clinical management of patients receiving GARFT inhibitors often involves folic acid and vitamin B12 supplementation to reduce the risk of severe hematologic and gastrointestinal toxicities [3].

Other names

Phosphoribosylglycinamide formyltransferaseGARTGAR transformylaseTrifunctional purine biosynthetic protein adenosine-3GARS-AIRS-GART5-phosphoribosylglycinamide formyltransferase

Inhibition of the transfer of a formyl group from 10-formyltetrahydrofolate to glycinamide ribonucleotide, thereby disrupting de novo purine biosynthesis and inhibiting DNA/RNA synthesis.