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Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate , as well as in pyrimidine nucleotide formation.
A key regulatory step is the production of 5-phospho-α-D-ribosyl 1-pyrophosphate by ribose-phosphate diphosphokinase, which is activated by inorganic phosphate and inactivated by purine ribonucleotides. It is not the committed step to purine synthesis because PRPP is also used in pyrimidine synthesis and salvage pathways.
Ribose 5-phosphate is produced by the pentose phosphate pathway from Glucose-6-Phosphate. The product phosphoribosyl pyrophosphate acts as an essential component of the purine salvage pathway and the de novo synthesis of purines. Dysfunction of the enzyme would thereby undermine purine metabolism.
Activation of ribose 5-phosphate to phosphoribosyl pyrophosphate by ribose-phosphate diphosphokinase. PRPP also plays an important role in pyrimidine ribonucleotide synthesis. During the fifth step of pyrimidine nucleotide synthesis, PRPP covalently links to orotate at the one-position carbon on the ribose unit.
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The enzyme phosphoribosyl pyrophosphate synthetase (PRS) catalyzes the formation of phosphoribosyl pyrophosphate which is a substrate for synthesis of purine and pyrimidine nucleotides, histidine, tryptophan and NAD. PRS exists as a complex with two catalytic subunits and two associated subunits.
The purine biosynthesis enzymes can be co-purified under certain conditions. [6] [7] A complex of two particular pathway enzymes GART and ATIC can be isolated with cofactor production enzyme C1THF synthase and SHMT1. [8]
The furanose (5-carbon) sugar in AIR comes from the pentose phosphate pathway, which converts glucose (as its 6-phosphate derivative) into ribose 5-phosphate (R5P). [10] The subsequent reactions which attach the amino imidazole portion of the molecule begin when R5P is activated as its pyrophosphate derivative, phosphoribosyl pyrophosphate (PRPP).