PRPP

PRPP, or 5-phosphoribosyl-1-pyrophosphate, is a highly activated form of ribose phosphate that serves as a donor of the ribose-5-phosphate moiety in nucleotide metabolism. It is produced from ribose-5-phosphate by the enzyme ribose-phosphate pyrophosphokinase (also called PRPP synthetase), using ATP and yielding PRPP and AMP.

In de novo purine biosynthesis, PRPP provides the prime substrate for the enzyme glutamine-PRPP amidotransferase, which incorporates the purine ring onto the activated ribose to form phosphoribosylamine and ultimately inosine monophosphate (IMP). In de novo pyrimidine biosynthesis, PRPP is used by orotate phosphoribosyltransferase to attach the ribose-phosphate to orotate, forming orotidine monophosphate (OMP). Thus PRPP links energy metabolism to the generation of both purine and pyrimidine nucleotides.

PRPP also participates in salvage pathways that recycle bases into nucleotides. Hypoxanthine and guanine are converted to IMP and GMP, and adenine to AMP, via hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT), respectively, with PRPP providing the ribose phosphate moiety.

Regulation and clinical relevance: PRPP levels are tightly controlled to balance nucleotide synthesis with cellular energy state and nucleotide pools. Dysregulation of PRPP metabolism can affect DNA and RNA synthesis. Mutations in PRPP synthetase genes or related regulatory mechanisms can lead to metabolic or neurological disorders, and excessive PRPP production has been linked to enhanced purine synthesis and disorders such as gout in some contexts.