De Novo Purine Synthesis

Summary

De novo purine synthesis is a biochemical pathway that creates purine nucleotides from simple molecules. This can be contrasted against purine salvage, which recycles purines nucleotides after partial degradation.

De novo purine synthesis begins with the precursor molecule Ribose-5-phosphate (R5P) . R5P is then converted to its high energy, "activated" form, PRPP . This form enables the transfer of phosphoribosyl groups (such as R5P). This R5P transferred from PRPP forms the pentose sugar of the eventual purine nucleotide.

Next, PRPP undergoes a series of reactions that require aspartate, glycine, THF, and glutamine. Through these steps, PRPP is converted into IMP (inosine monophosphate), the purine precursor molecule. The conversion of PRPP to IMP can be inhibited by the drug 6-MP (6-mercaptopurine) as well as by its prodrug azathioprine.

Finally, IMP can be converted to either AMP (adenosine monophosphate) or GMP (guanine monophosphate). The latter reaction is especially important, as the drugs mycophenolate and ribavirin inhibit the enzyme IMP dehydrogenase, which converts IMP to GMP.

Key Points

• De Novo Purine Synthesis
  • Common with De Novo Pyrimidine Synthesis and Purine Salvage
    • Ribose-5-P → PRPP
      • Catalyzed by PRPP synthetase
  • Specific to Purine Synthesis
    • PRPP → → → IMP
      • Requires aspartate, glycine, glutamine, and THF
      • Blocked by purine analog 6-MP (6-mercaptopurine) or its prodrug, azathioprine
    • IMP → GMP
      • catalyzed by IMP dehydrogenase
        • Inhibited by mycophenolate and ribavarin
    • IMP → AMP

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