Phosphoribosyl pyrophosphate (PRPP) (PRPP)

Phosphoribosyl pyrophosphate (PRPP) is a vital pentose sugar derivative that acts as a high-energy phosphate donor in various biosynthetic pathways [PubChem CID 7357]. It is synthesized from ribose 5-phosphate and ATP by the enzyme phosphoribosyl pyrophosphate synthetase (PRPS) [UniProt P60891]. PRPP is indispensable for the de novo synthesis of purine and pyrimidine nucleotides, as well as the salvage pathways that recycle free bases into nucleotides [StatPearls: Biochemistry, Purine Metabolism]. Beyond nucleotide metabolism, it is required for the synthesis of nicotinamide adenine dinucleotide (NAD+) [KEGG: map00230]. Clinical disorders associated with PRPP include gout and Lesch-Nyhan syndrome, which arise from the overproduction or impaired utilization of this molecule [NCBI: NBK1345]. In pharmacology, PRPP is not a direct drug target but is a critical substrate for the activation of several antimetabolite prodrugs, such as 6-mercaptopurine and 5-fluorouracil, which require PRPP for their conversion into active, cytotoxic nucleotide analogs [PubMed: 12110628]. Consequently, modulating PRPP levels or its utilization remains a strategic focus in treating hyperproliferative diseases and metabolic disorders.

Other names

5-Phosphoribosyl-1-pyrophosphatealpha-D-5-Phosphoribosyl-1-pyrophosphate5-Phospho-alpha-D-ribose 1-diphosphatePRPPP-Rib-PP

PRPP acts as a critical ribose-phosphate donor for the enzymatic activation of antimetabolite prodrugs (e.g., 6-mercaptopurine, 5-fluorouracil) into their active nucleotide forms, which then inhibit nucleic acid synthesis [PubMed: 12110628].