Phosphoribosyl pyrophosphate-utilizing enzyme (PRTase) (PRTase)

Phosphoribosyl pyrophosphate (PRPP)-utilizing enzymes, primarily known as phosphoribosyltransferases (PRTases), are a diverse group of enzymes essential for the biosynthesis of nucleotides and cofactors (UniProt, Family: Phosphoribosyltransferase). They catalyze the displacement of the pyrophosphate group of PRPP by a nucleophilic nitrogenous base, a reaction fundamental to both de novo and salvage pathways for purines and pyrimidines (PubChem, CID 7357). This class also includes enzymes critical for the production of nicotinamide adenine dinucleotide (NAD+), such as nicotinamide phosphoribosyltransferase (NAMPT). Due to their central role in cellular metabolism and proliferation, these enzymes are major therapeutic targets in oncology, where rapidly dividing cells require high nucleotide pools. Antimetabolite drugs like 5-fluorouracil and 6-mercaptopurine are activated by these enzymes into cytotoxic metabolites that inhibit DNA and RNA synthesis (PubMed, PMID: 15591023). Furthermore, inhibitors of NAMPT are being developed to deplete NAD+ levels, effectively starving cancer cells of energy and DNA repair capacity (PubMed, PMID: 18628525). Genetic deficiencies in specific PRTases, such as HGPRT, lead to severe metabolic disorders like Lesch-Nyhan syndrome, characterized by uric acid overproduction and neurological symptoms (NIH, GeneReviews: Lesch-Nyhan Syndrome). Overall, this enzyme family represents a cornerstone of metabolic pharmacology, bridging classic chemotherapy with modern targeted metabolic inhibitors.

Other names

PhosphoribosyltransferasesPRPP-dependent enzymesPRT familyPhosphoribosyltransferase

Competitive inhibition of substrate binding or metabolic activation of prodrugs into toxic nucleotide analogs that disrupt DNA and RNA synthesis (PubMed, PMID: 15591023).