De novo purine biosynthetic pathway (DNPS) (DNPS)

The de novo purine biosynthetic pathway is a fundamental metabolic process that constructs purine nucleotides, such as adenosine and guanosine, from basic precursors like amino acids and phosphoribosyl pyrophosphate (StatPearls, 2023). These nucleotides are essential for the synthesis of DNA and RNA, as well as for cellular energy metabolism and signaling (KEGG, 2024). Because rapidly proliferating cells, including cancer cells and activated immune cells, require a constant supply of nucleotides, this pathway is a critical target for therapeutic intervention (Nature Reviews Cancer, 2013). Drugs targeting this pathway, such as methotrexate and mycophenolate mofetil, work by inhibiting key enzymes like dihydrofolate reductase or inosine monophosphate dehydrogenase, thereby depleting the nucleotide pools necessary for cell division (PubMed, 2021). This inhibition leads to cell cycle arrest and is widely utilized in the treatment of malignancies and autoimmune diseases (NIH, 2022). Furthermore, the pathway's role in providing precursors for GTP makes it vital for G-protein signaling and protein synthesis (UniProt, 2023). Therapeutic challenges include the potential for systemic toxicity, as the pathway is also necessary for the maintenance of healthy, rapidly dividing tissues like the intestinal mucosa and bone marrow (StatPearls, 2023).

Other names

DNA/RNA and de novo purine synthesis pathwayPurine de novo synthesisPurine nucleotide biosynthetic processDe novo purine synthesis

Inhibition of rate-limiting enzymes (e.g., IMPDH, DHFR) and competitive antagonism of natural substrates by purine analogs to disrupt DNA and RNA synthesis.