Nucleic acid synthesis and nucleotide metabolism

Nucleic acid synthesis and nucleotide metabolism represent the collective biochemical processes involved in the creation, interconversion, and degradation of nucleotides, the fundamental units of genetic material (StatPearls, 2023). These pathways are divided into de novo synthesis, which builds nucleotides from basic metabolic precursors, and salvage pathways, which recover bases and nucleosides from degraded DNA and RNA (NIH, 2024). In clinical medicine, these pathways are primary targets for chemotherapy and immunosuppression because proliferating cells—such as tumor cells, bacteria, and viruses—require a constant supply of nucleotides for genome replication (PubMed, PMID: 31505148). Therapeutic agents targeting these processes, known as antimetabolites, typically function by inhibiting essential enzymes like dihydrofolate reductase (DHFR) or by mimicking natural nucleotides to cause DNA damage or chain termination (PubChem, 2024). Despite their efficacy, the lack of absolute specificity for diseased cells often leads to significant side effects in healthy, rapidly dividing tissues like the hematopoietic system and gastrointestinal tract (StatPearls, 2023). Furthermore, genetic variations in metabolic enzymes, such as TPMT or DPYD, can significantly impact drug toxicity and efficacy, necessitating biomarker-guided dosing in certain populations (NIH, 2023).

Other names

Nucleotide metabolismNucleic acid biosynthesisPurine and pyrimidine metabolic pathwaysNucleotide biosynthesis and salvage

Inhibition of rate-limiting enzymes in purine/pyrimidine synthesis (e.g., DHFR, Thymidylate synthase) or competitive inhibition of DNA/RNA polymerases via nucleoside analogs (StatPearls, 2023).