De novo purine biosynthetic pathway (DNPS)

The de novo purine biosynthetic pathway is a multi-step metabolic process that synthesizes purine nucleotides, specifically adenosine monophosphate (AMP) and guanosine monophosphate (GMP), from simple precursors like amino acids and bicarbonate (StatPearls: Purine Metabolism). This pathway is a critical component of cellular metabolism as it provides the essential building blocks for DNA replication and RNA transcription, making it indispensable for cell growth and proliferation (NCBI: Biochemistry). Because rapidly dividing cells, including cancer cells and activated lymphocytes, have a significantly higher demand for nucleotides than quiescent cells, the enzymes within this pathway are prime targets for therapeutic intervention (PubMed: PMID 25611108). Drugs such as methotrexate and mycophenolate mofetil exert their effects by inhibiting specific enzymes like dihydrofolate reductase or inosine monophosphate dehydrogenase, thereby starving the cell of the nucleotides required for genomic integrity (StatPearls: Methotrexate; StatPearls: Mycophenolate). Consequently, targeting this pathway is a standard strategy in oncology for treating leukemias and solid tumors, as well as in rheumatology and transplant medicine to suppress unwanted immune responses (StatPearls: Mercaptopurine).

Other names

DNA synthesis / de novo purine synthesisPurine metabolismDe novo purine biosynthesisPurine nucleotide synthesis

Inhibition of key enzymes within the de novo purine biosynthetic pathway, such as dihydrofolate reductase (DHFR) and inosine monophosphate dehydrogenase (IMPDH), leading to the depletion of purine nucleotide pools and subsequent arrest of DNA and RNA synthesis.