Legend: ADP: Adenosine Diphosphate; AMP: Adenosine Monophosphate; CDP: cytidine Diphosphate; CTP: Cytidine Triphosphate; dCDP: Deoxycytidine Diphosphate; DHFR: dihydrofolate Reductase; dTMP: Deoxythimidine Monophosphate; dUDP: Deoxyuridine Diphosphate; dUMP: Deoxyuridine Monophosphate; GDP: Guanine Diphosphate; GMP: Guanine Monophosphate; HGPRT: Hypoxanthine-Guanine Phosphoribosyltransferase; IMP: inosine monophosphate; Methyl THF: Methyltetrahydrofolate; MTX: Methotrexate; PNP: Purine Nucleotide Phosphorylase; PRPP: Phosphoribosyl Pyrophosphate; UDP: Uracil Diphosphate; UMP: Uracil Monophosphate; UTP: uracil Triphosphate; XMP: Xanthine Monophosphate
Figure 1: Effects of methotrexate on folate metabolism in relation to nucleotide metabolism. Via its inhibition of dihydrofolate reductase, methotrexate interferes with the generation of tetrahydrofolate and subsequently, DNA synthesis. Tetrahydrofolate is metabolized further for use as a cofactor in the synthesis of dTMP. Folinic acid, leuvovorin, is often used to rescue cells from methotrexate and restore cellular stores of tetrahydrofolate. In addition to interference with DNA synthesis, this diagram superficially shows the involvement of tetrahydrofolate in the metabolism of purines.