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[1] [2] [3] The vitamins thiamine [4] and cobalamin, [5] and the amino acid tryptophan also contain fragments derived from PRPP. [6] It is formed from ribose 5-phosphate (R5P) by the enzyme ribose-phosphate diphosphokinase: [7] It plays a role in transferring phospho-ribose groups in several reactions, some of which are salvage pathways: [8]
Ribose-phosphate diphosphokinase transfers the diphosphoryl group from Mg-ATP (Mg 2+ coordinated to ATP) to ribose 5-phosphate. [2] The enzymatic reaction begins with the binding of ribose 5-phosphate, followed by binding of Mg-ATP to the enzyme. In the transition state upon binding of both substrates, the diphosphate is transferred.
Ribose 5-phosphate (R5P) is both a product and an intermediate of the pentose phosphate pathway. The last step of the oxidative reactions in the pentose phosphate pathway is the production of ribulose 5-phosphate. Depending on the body's state, ribulose 5-phosphate can reversibly isomerize to ribose 5-phosphate.
Amidophosphoribosyltransferase (ATase), also known as glutamine phosphoribosylpyrophosphate amidotransferase (GPAT), is an enzyme responsible for catalyzing the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosyl-1-amine (PRA), using the amine group from a glutamine side-chain.
The pathway begins with the conversion of Ribose-5-Phosphate(R5P) to phosphoribosyl pyrophosphate (PRPP) by enzyme ribose-phosphate diphosphokinase (PRPS1). PRPP is then converted to 5-phosphoribosylamine (5-PRA) as glutamine donates an amino group to the C-1 of PRPP.
IMP is synthesized de novo from glucose through the pentose phosphate pathway which produces ribose 5-P, which then converts to PRPP that with the amino acids glycine, glutamine, and aspartate (see Purine metabolism) can be further converted into IMP. [7]
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.
Beta-D-ribofuranose can then be converted to ribose-5-phosphate. In the images on the right, both structures have five carbons but differ in the amount of hydrogens by one, oxygens by three, and phosphorus by one. The key difference is the group on carbon four. From here, ribose 5-phosphate can enter into the pentose phosphate pathway (PPP). [4]