Multiple nucleotide metabolism and nucleic acid synthesis pathway

Multiple nucleotide metabolism and nucleic acid synthesis pathway encompasses the complex network of biochemical reactions responsible for creating purine and pyrimidine nucleotides, which serve as the building blocks for DNA and RNA (StatPearls, 2023). These pathways include de novo synthesis from simple precursors and salvage pathways that recycle pre-formed bases (NCBI, 2022). Because rapidly dividing cells, such as cancer cells and activated immune cells, have a high demand for nucleotides, these pathways are critical therapeutic targets (Nature Reviews Cancer, 2017). Drugs targeting these processes, known as antimetabolites, typically inhibit key enzymes like dihydrofolate reductase (DHFR), thymidylate synthase (TS), or ribonucleotide reductase (RNR), or act as fraudulent bases that disrupt nucleic acid integrity (PubMed, 2021). However, because these pathways are fundamental to all proliferating cells, therapeutic intervention often results in systemic toxicities, particularly in the bone marrow and gut epithelium (NIH, 2023).

Other names

Nucleotide metabolismPurine and pyrimidine biosynthesisNucleic acid synthesisAntimetabolite pathways

Drugs targeting these pathways function as antimetabolites that inhibit key enzymes such as dihydrofolate reductase (DHFR), thymidylate synthase (TS), inosine monophosphate dehydrogenase (IMPDH), or ribonucleotide reductase (RNR), or act as nucleotide analogs that incorporate into DNA/RNA to cause chain termination (StatPearls, 2023; PubMed, 2021).