Nucleotide synthesis enzymes and pathways

Nucleotide synthesis enzymes and pathways encompass the complex biochemical processes responsible for the production of purine and pyrimidine nucleotides, which are essential building blocks for DNA and RNA (StatPearls: Purine and Pyrimidine Metabolism). These pathways include both de novo synthesis, which builds nucleotides from simple precursors like amino acids and carbon dioxide, and salvage pathways, which recycle nucleobases and nucleosides from degraded nucleic acids (NCBI: Purine Metabolism). Because rapidly dividing cells, such as cancer cells and activated immune cells, have a high demand for nucleotides to support DNA replication and transcription, these enzymes are critical therapeutic targets (PubMed: Nucleotide metabolism in cancer). Drugs targeting these pathways, such as antimetabolites, work by inhibiting key enzymes like dihydrofolate reductase (DHFR) or thymidylate synthase (TS), thereby depleting the cellular nucleotide pool and inducing cell cycle arrest or apoptosis (NCBI: Antimetabolites). Beyond oncology, these pathways are targeted in the treatment of autoimmune disorders and viral infections to limit the proliferation of pathological cells or the replication of viral genomes (PubMed: IMPDH as a drug target).

Other names

Purine and pyrimidine metabolismNucleotide biosynthesisDe novo nucleotide synthesisNucleotide salvage pathwaysNucleotide metabolism

Inhibition of specific rate-limiting enzymes within the purine and pyrimidine synthesis pathways to deplete intracellular nucleotide pools, thereby preventing DNA and RNA synthesis and inducing cell cycle arrest or apoptosis (NCBI: Antimetabolites).