Nucleotide metabolism

Nucleotide metabolism encompasses the complex biochemical pathways responsible for the synthesis, interconversion, and degradation of purines and pyrimidines, which serve as the essential building blocks for DNA and RNA (StatPearls, 2023). Beyond genetic storage, nucleotides are critical for cellular energy metabolism via ATP and GTP, and they act as key secondary messengers in signal transduction pathways (NCBI, 2022). Because rapidly proliferating cells, such as malignant cancer cells and activated immune cells, have an exceptionally high demand for nucleotides to support division, enzymes within these pathways are frequent targets for therapeutic intervention (Nature Reviews Cancer, 2021). Drugs known as antimetabolites, such as methotrexate and 5-fluorouracil, work by inhibiting specific enzymes like dihydrofolate reductase or thymidylate synthase to deplete nucleotide pools and halt cell cycle progression (PubMed, 2020). While highly effective in treating cancer and autoimmune diseases, targeting these fundamental pathways often results in significant clinical toxicities, particularly in other fast-dividing tissues like the bone marrow and gastrointestinal mucosa (StatPearls, 2023).

Other names

Purine and pyrimidine metabolismNucleotide biosynthesisNucleotide salvage pathwayNucleotide degradation

Inhibition of rate-limiting enzymes in the de novo or salvage pathways of purine and pyrimidine synthesis, leading to depletion of nucleotide pools and subsequent inhibition of nucleic acid synthesis and cell division.