phosphoribosylglycinamide

Phosphoribosyl refers to chemical groups that contain a ribose-5-phosphate moiety, often linked to a phosphate group. In biochemistry the most prominent example is phosphoribosyl pyrophosphate (PRPP), an activated form of ribose-5-phosphate that serves as a central substrate in nucleotide metabolism.

PRPP is formed from ribose-5-phosphate by the enzyme ribose-phosphate pyrophosphokinase (PRPP synthetase) in an ATP-dependent reaction. It functions as a key junction in the biosynthesis and salvage of nucleotides, providing the ribose-phosphate backbone for both purine and pyrimidine pathways. PRPP is also involved in the biosynthesis of certain amino acids, notably histidine and tryptophan, in many microorganisms.

In purine biosynthesis, PRPP donates its ribose-phosphate unit in reactions that commit the pathway toward the formation of inosine monophosphate and downstream nucleotides. In pyrimidine synthesis, orotate phosphoribosyltransferase uses PRPP to generate orotidine-5'-phosphate, a precursor to uridine monophosphate. In salvage pathways, phosphoribosyltransferases reuse bases by transferring the phosphoribosyl group from PRPP to the base, regenerating nucleotides without de novo synthesis.

Regulation of PRPP availability integrates cellular energy status and nucleotide pools, reflecting metabolic needs. Abnormalities in PRPP metabolism or its enzymes can disrupt nucleotide balance and are relevant to certain metabolic disorders and gout. Because of its central role, PRPP and related phosphoribosyltransferases are common targets of biochemical study and pharmacological interest, with implications for cancer and antimicrobial research.