The pathway for synthesis of inosine monophosphate (IMP), the parent purine nucleotide, is described below:

  1. Ribose 5-phosphate produced in the hexose monophosphate shunt is the starting material of purine nucleotide synthesis. It reacts with ATP to form phosphoribosyl pyrophosphate (PRPP).
  2. Glutamine transfers its amide nitrogen to phosphoribosyl pyrophosphate to replace pyrophosphate and produce 5-phosphoribosylamine. The enzyme phosphoribosyl pyrophosphate glutamyl amidotransferase is controlled by feedback inhibition of nucleotides (IMP, AMP, and GMP). This reaction is the committed step in purine nucleotide biosynthesis.
  3. Phosphoribosylamine reacts with glycine in the presence of ATP to form glycinamide ribosyl 5-phosphate or glycinamide ribotide (GAR).
  4. N10 -formyltetrahydrofolate donates the formyl group, and the product formed is formyl glycinamide ribosyl 5-phosphate.
  5. Glutamine transfers the second amido amino group to produce formyl glycinamidine ribosyl 5-phosphate.
  6. The imidazole ring of the purine is closed; an ATP-dependent reaction yields 5-amino-imidazole ribosyl 5-phosphate.
  7. Incorporation of CO2 (carboxylation) occurs yield aminoimidazole carboxylate ribosyl 5-phosphate. The reaction does not require vitamin biotin and ATP; this is the case with most of the carboxylation reactions.
  8. Aspartate condenses with the product in reaction 7 to form amino imidazole 4-succinyl carboxamide ribosyl 5-phosphate.
  9. Adenylosuccinate lyase cleaves off fumarate and only the amino group of aspartate is retained to yield aminoimidazole 4-carboxamide ribosyl 5-phosphate.
  10. N10-formyltetrahydrofolate donates a one-carbon moiety to produce formaminoimidazole 4-carboxamide ribosyl 5-phosphate, with this reaction; all the carbon and nitrogen atoms of purine ring are contributed by the respective sources.
  11. The final reaction catalysed by cyclohydrase leads to ring closure with an elimination of water molecule. The product obtained is inosine monophosphate (IMP), from which other purine nucleotides can be synthesised. Synthesis of purine nucleotides in Figure 11.2.

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