Cellular nucleic acid synthesis pathways

Cellular nucleic acid synthesis pathways encompass the essential biochemical processes responsible for producing the purine and pyrimidine nucleotides required for DNA replication and RNA transcription [3, 5]. These pathways include de novo synthesis from simple precursors like amino acids and sugars, as well as salvage pathways that recycle preformed nucleosides [1, 5]. Because rapidly dividing cells, such as malignant tumor cells and activated lymphocytes, have a significantly higher demand for nucleotides, these pathways are primary targets for chemotherapy and immunosuppressive therapy [3, 4]. Key enzymatic targets within these pathways include dihydrofolate reductase (DHFR), thymidylate synthase, and inosine monophosphate dehydrogenase (IMPDH) [1, 2]. Drugs targeting these pathways, often referred to as antimetabolites, function by inhibiting these enzymes or by acting as fraudulent building blocks that disrupt nucleic acid integrity and trigger apoptosis [5]. However, the lack of absolute specificity for diseased cells often leads to significant side effects in healthy, high-turnover tissues like the bone marrow and intestinal epithelium [3, 4].

Other names

Nucleotide biosynthesis pathwaysDNA synthesis pathwayRNA synthesis pathwayNucleic acid metabolismDe novo nucleotide synthesis

Inhibition of rate-limiting enzymes in purine and pyrimidine biosynthesis (e.g., DHFR, DHODH, IMPDH), competitive inhibition of DNA or RNA polymerases, and the incorporation of antimetabolites into nascent nucleic acid chains leading to chain termination or lethal mutagenesis [1, 2, 5].