Cellular nucleic acids and nucleotide metabolism

Cellular nucleic acids and nucleotide metabolism refers to the integrated network of biochemical pathways responsible for the synthesis, interconversion, and degradation of nucleotides and their polymers, DNA and RNA (Reactome ID: R-HSA-158699). This system is fundamental to life, providing the essential building blocks for genetic information storage, energy transfer via ATP, and intracellular signaling. In many diseases, particularly cancer and viral infections, these pathways are hijacked or upregulated to support rapid proliferation and replication, making them a primary focus for therapeutic intervention (NCBI, 2023). Pharmacological agents, known as antimetabolites, target specific enzymes within these pathways—such as dihydrofolate reductase or thymidylate synthase—to deplete nucleotide pools or introduce errors into the genetic code. While highly effective, these treatments often carry significant risks of systemic toxicity because they affect all rapidly dividing cells in the body, including those in the bone marrow and gut (PubMed, 2022). Consequently, this entry describes a broad biological process and a category of drug targets rather than a single molecular entity (StatPearls, 2023).

Other names

Nucleotide metabolismNucleic acid metabolismPurine and pyrimidine metabolismNucleotide biosynthesis and degradation

Drugs targeting this pathway act as antimetabolites by inhibiting key enzymes (e.g., dihydrofolate reductase, thymidylate synthase, inosine monophosphate dehydrogenase) or by serving as nucleoside analogs that incorporate into DNA/RNA, leading to chain termination, DNA damage, or inhibition of polymerases (StatPearls, 2023; PubChem, 2024).