Purine de novo synthesis enzymes (DNPS enzymes)

The purine de novo synthesis enzymes are a group of six proteins that catalyze the ten-step metabolic pathway converting 5-phosphoribosyl-1-pyrophosphate (PRPP) into inosine monophosphate (IMP). In humans, these enzymes include amidophosphoribosyltransferase (PPAT), the trifunctional GART protein, phosphoribosylformylglycinamidine synthase (PFAS), the bifunctional PAICS protein, adenylosuccinate lyase (ADSL), and the bifunctional ATIC protein. These enzymes often cluster into a dynamic multi-enzyme complex known as the purinosome to increase pathway efficiency and protect reactive intermediates. This pathway is essential for providing the building blocks for DNA and RNA synthesis, particularly in rapidly proliferating cells such as cancer cells and activated immune cells. Consequently, these enzymes are major therapeutic targets for antimetabolite chemotherapy and immunosuppressive drugs, which act by depleting cellular purine pools and inducing cell cycle arrest or apoptosis.

Other names

Purine biosynthetic pathway enzymesPurinosome enzymesDe novo purine nucleotide biosynthesis enzymesPDNS enzymesDNPS enzymes

Inhibition of specific enzymes in the purine de novo synthesis pathway (e.g., PPAT, GART, ATIC, or IMPDH), leading to the depletion of intracellular purine nucleotide pools (ATP and GTP), which impairs DNA and RNA synthesis and results in cell cycle arrest and apoptosis.