Purine synthesis enzymes and purine-dependent metabolic pathways

Purine synthesis enzymes and purine-dependent metabolic pathways are essential for the production of adenine and guanine nucleotides, which serve as the building blocks for DNA and RNA [1.3.1]. These pathways include the de novo synthesis pathway, which builds the purine ring from simple precursors like amino acids and one-carbon donors, and the salvage pathway, which recycles pre-formed purine bases [1.1.4, 1.3.5]. Because rapidly dividing cells, such as cancer cells and activated lymphocytes, have a high demand for nucleotides, these enzymes are critical therapeutic targets in oncology and immunology [1.1.1, 1.2.1]. Drugs targeting these pathways, such as methotrexate and mycophenolate mofetil, work by depleting the cellular pool of nucleotides or incorporating fraudulent analogs into nucleic acids, thereby inhibiting cell proliferation [1.2.3, 1.2.5]. Additionally, defects in purine metabolism are linked to metabolic disorders like gout and Lesch-Nyhan syndrome, making these pathways vital for maintaining physiological homeostasis [1.3.2, 1.4.1].

Other names

Purine metabolismPurine biosynthetic pathwayDe novo purine synthesisPurine salvage pathwayPurinosome

Inhibition of de novo purine synthesis enzymes (e.g., IMPDH, DHFR, GARFT), inhibition of purine salvage, incorporation of purine analogs into DNA/RNA to cause strand breaks, and inhibition of xanthine oxidase to reduce uric acid production.