Nucleotide metabolism in AML and relevant therapeutic strategies. (A) Purine nucleotide biosynthesis in AML. Schematic representation showing purine synthesis through the utilization of glycolytic intermediates. Key enzymes, inhibitory compounds, and metabolic pathways with demonstrated relevance to AML pathophysiology are highlighted in blue, red, and pink, respectively. (B) Pyrimidine nucleotide biosynthesis in AML. Schematic representation showing the key enzymes involved in de novo pyrimidine synthesis. The transport of pyrimidine analog cytarabine and the mechanistic inhibition of DNA synthesis in leukemic cells is represented. Different enzymes, inhibitory compounds, and metabolic pathways with demonstrated relevance to AML pathophysiology are highlighted in blue, red, and pink, respectively. Ara-U, uracil arabinoside; CDP, cytidine diphosphate; CMP, cytarabine monophosphate; CTP, cytidine triphosphate; DHF, dihydrofolate; DHFR, dihydrofolate reductase; DOODH, dihydroorotate dehydrogenase; GMP, guanine monophosphate; IMP, inosine monophosphate; IMPDH, 5′-monophosphate dehydrogenase; OMP, orotidine 5′-monophosphate; 3-PG, 3-phosphoglycerate; PHGDP, 3-phosphoglycerate dehydrogenase; PPP, pentose phosphate pathway; 6-TG; 6-thioguanine; UMP, uridine monophosphate; TS, thymidylate synthase; UDP, uridine diphosphate; UTP, uridine triphosphate; XMP, xanthine monophosphate.