Purine biosynthesis enzymes and nucleic acids

Purine biosynthesis enzymes and nucleic acids represent a complex of therapeutic targets involved in the production and utilization of purine nucleotides. The de novo purine biosynthetic pathway consists of ten enzymatic steps that convert phosphoribosyl pyrophosphate (PRPP) into inosine monophosphate (IMP), which is then converted into AMP and GMP (NCBI, NBK22404). Key enzymes in this pathway, such as inosine monophosphate dehydrogenase (IMPDH) and phosphoribosylpyrophosphate amidotransferase (PPAT), are critical for maintaining the nucleotide pools required for cellular processes (PubMed, 28673520). Drugs targeting these enzymes, such as mycophenolate mofetil and methotrexate, disrupt the supply of nucleotides, thereby inhibiting DNA replication and RNA synthesis (StatPearls, NBK553087). Additionally, purine antimetabolites like 6-mercaptopurine and 6-thioguanine act as structural analogs; they are metabolized into triphosphate forms and incorporated directly into DNA and RNA (DrugBank, DB01033). This incorporation leads to the termination of chain elongation, mismatch repair activation, and eventual apoptosis (PubMed, 30553480). This multi-faceted targeting is particularly effective in rapidly dividing cells, making these pathways primary targets for chemotherapy in leukemias and for immunosuppression in autoimmune diseases.

Other names

Purine metabolism pathwayPurine antimetabolite targetsDe novo purine biosynthetic pathwayPurine salvage pathway

Inhibition of enzymes in the purine biosynthetic pathway and incorporation of fraudulent nucleotide analogs into DNA and RNA to disrupt synthesis and function.