Purine metabolism

Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which is the first compound in the pathway to have a completely formed purine ring system.

A key regulatory step is the production of 5-phospho-α-D-ribosyl 1-pyrophosphate (PRPP) by ribose-phosphate diphosphokinase, which is activated by inorganic phosphate and inactivated by purine ribonucleotides.

Due to the chemical lability of PRA, which has a half-life of 38 seconds at PH 7.5 and 37 °C, researchers have suggested that the compound is channeled from amidophosphoribosyltransferase to GAR synthetase in vivo.

When a defective gene causes gaps to appear in the metabolic recycling process for purines and pyrimidines, these chemicals are not metabolised properly, and adults or children can suffer from any one of twenty-eight hereditary disorders, possibly some more as yet unknown.

Symptoms can include gout, anaemia, epilepsy, delayed development, deafness, compulsive self-biting, kidney failure or stones, or loss of immunity.

Purine metabolism can have imbalances that can arise from harmful nucleotide triphosphates incorporating into DNA and RNA which further lead to genetic disturbances and mutations, and as a result, give rise to several types of diseases.

Mycophenolate mofetil is an immunosuppressant drug used to prevent rejection in organ transplantation; it inhibits purine synthesis by blocking inosine monophosphate dehydrogenase (IMPDH).

[5] Methotrexate also indirectly inhibits purine synthesis by blocking the metabolism of folic acid (it is an inhibitor of the dihydrofolate reductase).

Nam et al.[6] demonstrated the direct condensation of purine and pyrimidine nucleobases with ribose to give ribonucleosides in aqueous microdroplets, a key step leading to RNA formation.