The purine nucleotide synthesis is well coordinated to meet the cellular demands. The intracellular concentration of PRPP regulates purine synthesis to a large extent. This increase depends on the availability of ribose 5′-phosphate and the enzyme PRPP synthase. PRPP glutamyl amidotransferase is controlled by a feedback mechanism by purine nucleotides. That is, if AMP and GMP are available in adequate amounts to meet the cellular requirements, their synthesis is turned off at the amidotransferase reaction. Another important stage of regulation is in the conversion of IMP to GMP and AMP. AMP inhibits adenylsuccinate synthase, while GMP inhibits IMP DHase. Thus, AMP and GMP control their respective synthesis from IMP by feedback mechanism as described in Figure 11.4.

Figure 11.4 Regulation of Purine Nucleotides Synthesis