Nucleotide metabolism pathways (NMP)

Nucleotide metabolism pathways encompass the complex network of biochemical reactions responsible for the de novo synthesis, salvage, and degradation of purine and pyrimidine nucleotides (PubMed: 29440421). These pathways are essential for providing the building blocks for DNA and RNA replication, as well as maintaining cellular energy stores (ATP/GTP) and signaling molecules (cAMP) (NCBI: NBK22421). In rapidly proliferating cells, such as cancer cells or activated immune cells, the demand for nucleotides increases significantly, making these pathways prime targets for therapeutic intervention (Nature Reviews Cancer: 10.1038/s41568-019-0120-5). Drugs targeting specific enzymes within these pathways, such as dihydrofolate reductase or thymidylate synthase, are widely used in oncology and rheumatology to arrest cell growth and induce apoptosis (StatPearls: NBK532915). However, because these pathways are also active in healthy tissues, treatment often results in significant side effects like myelosuppression and mucosal damage (PubMed: 15591222). Dysregulation of these pathways is also linked to metabolic disorders like gout and various primary immunodeficiencies (PubMed: 21575513).

Other names

Purine and pyrimidine metabolismNucleotide biosynthesis and degradationNucleotide salvage pathwayDe novo nucleotide synthesis

Inhibition of specific rate-limiting enzymes within the de novo or salvage pathways (e.g., DHFR, IMPDH, Thymidylate synthase) to deplete cellular nucleotide pools, thereby disrupting nucleic acid synthesis and inducing cell cycle arrest or apoptosis (StatPearls: NBK532915).