DNA synthesis machinery via nucleotide metabolism

The DNA synthesis machinery via nucleotide metabolism refers to the integrated network of enzymes and metabolic pathways that produce deoxyribonucleotides (dNTPs) and utilize them for DNA replication. This system includes de novo synthesis and salvage pathways for purines and pyrimidines, featuring essential enzymes such as dihydrofolate reductase (DHFR), thymidylate synthase (TS), and ribonucleotide reductase (RNR) (NCBI, 2023). These enzymes ensure the availability of dNTP pools, which are then polymerized into new DNA strands by DNA polymerases during the S-phase of the cell cycle. In many diseases, particularly cancer and viral infections, these pathways are hyperactivated to facilitate rapid genomic duplication (PubMed, 2022). Therapeutic intervention typically involves antimetabolites that act as competitive inhibitors of these enzymes or nucleoside analogs that incorporate into DNA to cause chain termination (StatPearls, 2023). While highly effective at stopping proliferation, these drugs often lack specificity for diseased cells, leading to significant side effects in high-turnover healthy tissues like the bone marrow and gastrointestinal tract (NIH, 2024).

Other names

Nucleotide biosynthesis pathwayDNA replication machineryAntimetabolite target pathwayDe novo nucleotide synthesis

Inhibition of key enzymes in nucleotide metabolism (e.g., DHFR, TS, RNR) or the use of nucleoside analogs to inhibit DNA polymerase and cause DNA chain termination (StatPearls, 2023; NIH, 2024).