Products of one-carbon metabolism are underlined. Lometrexol and LY309887 inhibit GARFT. Pemetrexed primarily inhibits TS, but also inhibits other folate-dependent enzymes shown within dashed boxes. DHF, dihydrofolate; THF, tetrahydrofolate; MTHFS, methenyltetrahydrofolate synthetase; cSHMT, cytoplasmic serine hydroxymethyltransferase; GARFT, glycinamide ribonucleotide formyltransferase; AICARFT, phosphoribosylaminoimidazole carboxamide formyltransferase; DHFR, dihydrofolate reductase; TS, thymidylate synthase.