PRPPdependent

PRPP-dependent refers to enzymes that utilize 5-phosphoribosyl-1-pyrophosphate (PRPP) as a substrate in nucleotide metabolism. PRPP provides the ribose-5-phosphate moiety in both de novo and salvage pathways for purine and pyrimidine nucleotides, linking nucleotide synthesis to cellular energy and carbon flux.

PRPP is produced from ribose-5-phosphate by phosphoribosyl pyrophosphate synthetase, using ATP. PRPP levels are tightly regulated and can be influenced by the cellular demand for nucleotides, the energy state of the cell, and feedback from purine nucleotides. Enzymes that consume PRPP in various salvage and biosynthetic reactions help maintain nucleotide pools and balance.

Examples of PRPP-dependent enzymes include those in purine salvage, such as hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT), which attach PRPP to hypoxanthine/guanine or adenine to form IMP, GMP, or AMP. In de novo purine synthesis, glutamine-PRPP amidotransferase (GPAT) uses PRPP in the first committed step to form phosphoribosylamine. In pyrimidine metabolism, orotate phosphoribosyltransferase (OPRT) uses PRPP to convert orotate to orotidine-5′-phosphate, and uracil phosphoribosyltransferase (UPRT) can function similarly in some organisms.

The term PRPP-dependent highlights the reliance of these enzymes on PRPP as a substrate, reflecting PRPP’s central role in nucleotide biosynthesis and salvage. Disruptions in PRPP metabolism can affect nucleotide balance and cellular proliferation, and the pathway is a focus of research for therapeutic targeting in cancer and infectious diseases.