Phosphoribosyl pyrophosphate

Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate that plays a critical role in both the biosynthesis of nucleotides and the amino acid salvage pathways. It is a crucial compound in cellular metabolism and is involved in the synthesis of purine and pyrimidine nucleotides, NAD, and amino acids such as histidine and tryptophan.

Biosynthesis

PRPP is synthesized from Ribose-5-phosphate by the action of the enzyme phosphoribosyl pyrophosphate synthetase (PRPP synthetase). This reaction involves the transfer of pyrophosphate from ATP to ribose-5-phosphate, resulting in the formation of PRPP and AMP. The synthesis of PRPP is a key regulatory step in the purine and pyrimidine nucleotide biosynthesis pathways.

Function

The primary function of PRPP is to act as a sugar donor in the synthesis of nucleotides and certain amino acids. In the purine biosynthesis pathway, PRPP reacts with glutamine through the action of amidophosphoribosyltransferase, initiating the formation of the purine nucleotide base. In the pyrimidine biosynthesis pathway, PRPP provides the ribose-phosphate backbone to which the pyrimidine base is attached.

Additionally, PRPP is involved in the salvage pathways of nucleotide biosynthesis, where it serves to reactivate bases by attaching a ribose-phosphate group to form nucleotides directly. This is crucial for the efficient use of free bases and nucleosides that are released during nucleic acid degradation.

Regulation

The synthesis and utilization of PRPP are tightly regulated to ensure a balanced supply of nucleotides for DNA and RNA synthesis. The activity of PRPP synthetase is regulated by feedback inhibition by purine nucleotides (such as ADP and GDP) and by allosteric activation by inorganic phosphate. This ensures that PRPP levels are adjusted according to the cellular demand for nucleotides.

Clinical Significance

Alterations in PRPP levels or the activity of PRPP synthetase can lead to disorders of purine metabolism, such as gout and certain types of anemia. Overactivity of PRPP synthetase can result in excessive purine synthesis, leading to hyperuricemia and gout. Conversely, deficiencies in PRPP synthetase activity can impair nucleotide biosynthesis, resulting in cellular dysfunction and disease.

See Also

• Nucleotide
• Purine metabolism
• Pyrimidine metabolism
• Gout
• Anemia