Multiple nucleotide metabolism enzymes and nucleic acid polymerases

Multiple nucleotide metabolism enzymes and nucleic acid polymerases represent a broad functional class of proteins essential for the synthesis, regulation, and polymerization of DNA and RNA building blocks (StatPearls, 2023). This group includes key metabolic enzymes like dihydrofolate reductase (DHFR) and thymidylate synthase (TS), which are essential for de novo nucleotide synthesis, as well as DNA and RNA polymerases that catalyze the assembly of polynucleotide chains (UniProt, 2024). These enzymes are critical for cellular proliferation and are frequently overexpressed or hijacked in diseases such as cancer and viral infections (Nature Reviews Drug Discovery, 2021). Pharmacological intervention typically involves antimetabolites, such as methotrexate or 5-fluorouracil, which inhibit metabolic flux, or nucleoside analogs like remdesivir and acyclovir, which act as chain terminators during nucleic acid synthesis (PubMed, 2022). Because these processes are fundamental to all living cells, drugs targeting this group often exhibit a narrow therapeutic index, with common toxicities including myelosuppression and gastrointestinal distress (NIH, 2023).

Other names

Nucleotide metabolism enzymesNucleic acid polymerasesDNA and RNA synthesis enzymesNucleotide biosynthetic enzymesPurine and pyrimidine metabolic enzymes

Drugs targeting this group typically act as antimetabolites that inhibit enzymes in the de novo or salvage nucleotide synthesis pathways, or as nucleoside/nucleotide analogs that compete with natural substrates for incorporation into nucleic acid chains by polymerases, leading to chain termination or lethal mutagenesis (PubMed, 2022; StatPearls, 2023).