5phosphoribosyl1pyrophosphate

5-phosphoribosyl-1-pyrophosphate, commonly abbreviated PRPP, is a ribose phosphate molecule that acts as an activated ribose donor in nucleotide metabolism. Structurally it is ribose-5-phosphate with a pyrophosphate group at the 1' position and a single phosphate at the 5' position.

Biosynthesis and location: PRPP is formed from ribose-5-phosphate by the enzyme ribose-phosphate pyrophosphokinase (PRPP synthetase) using ATP. This reaction occurs in the cytosol and represents a key control point in the supply of activated ribose for nucleotide production.

Roles in metabolism: PRPP is a central substrate for the de novo synthesis of nucleotides and for salvage pathways. In purine biosynthesis, it provides the ribose-phosphate moiety for the formation of phosphoribosylamine via glutamine-PRPP amidotransferase. In pyrimidine biosynthesis, orotate phosphoribosyltransferase uses PRPP to form orotidine-5'-phosphate. PRPP is also used in purine salvage by enzymes such as APRT and HGPRT to generate AMP and GMP. In histidine biosynthesis, ATP phosphoribosyltransferase uses PRPP to produce phosphoribosyl-ATP; in tryptophan biosynthesis, anthranilate phosphoribosyltransferase likewise utilizes PRPP.

Physiological significance and regulation: The cellular PRPP pool influences the capacity for nucleotide and amino acid production and thus cell growth and proliferation. Dysregulation of PRPP metabolism can contribute to disease, including gout due to overactivity of PRPP synthetase and altered purine synthesis in conditions such as HGPRT deficiency.