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Biosynthesis Of Purine Nucleotides


  1. De-Novo synthesis                      
  2. Salvage pathway
  1. De-Novo pathway
    1. Free Purine ring is not synthesized. Directly a nucleotide is formed as IMP.
    2. Inosine monophosphate is parent nucleotide from which AMP & GMP are formed.
    3. Synthesis of IMP occurs on Ribose -5- Phosphate and involves linear sequence of 11 reactions.
    4. The sources of carbon & nitrogen atoms of Purine ring in de-novo is:

        N1            –      Aspartate

        C2             –      N10-formyl Tetrahydrofolate

        N3, N9       –      Amide nitrogen of glutamine

        C4, C5, N7  –      Glycine

        C6             –      CO2

        C8             –      N5, N10 methylene tetrahydrofolate



  1. Salvage pathway



  1. Regulation of Purine nucleotide biosynthesis
    1. PRPP pool size regulates Purine nucleotide biosynthesis.
    2. AMP & GMP feedback regulate PRPP Glutamyl aminotransferase.
    3. AMP & GMP feedback regulate their formation from IMP.     
      1. Dietary Purines and pyrimidines are not incorporated into tissue nucleic acids.
      2. Humans biosynthesize Purines and pyrimidines from amphibolic intermediates.
      3. Their biosynthesis is precisely regulated and coordinated by feed back mechanism that ensures their production in appropriate quantities and according to varying physiological demands.
      4. Purine deficiency states are primarily due to deficiency of folic acid.
      5. Salvage reactions convert purines and their nucleosides to mononucleotides.
      6. Salvage means to save, rescue.
      7. PRPP pool size regulates purine nucleotide biosynthesis.
      8. AMP and GMP feed back regulate PRPP glutamyl aminotransferase. PRPP Glutamyl aminotransferase is a committed enzyme of denovo purine synthesis.
      9. NDP’s form dNDP’s using ribonucleotide reductase complex..
      10. UMP is the first true pyrimidine nucleotide synthesized de-novo. However the first pyrimidine ring is OROTATE & first pyrimidine nucleotide is OMP.
      11. Humans catabolize purines to uric acid.
      12. Net excretion of uric acid in humans is 400-600 mg/day.
      13. In mammals other than higher primates the enzyme uricase cleaves uric acid forming Allantoin
Extra Edge
  1. Several reactions of IMP biosynthesis require folate derivatives and glutamine. Consequently antifolate drugs and glutamine analogs inhibit purine biosynthesis
  2. Oxidation and amination of IMP forms AMP and GMP, and subsequent phosphory1 transfer from ATP to GDP forms GTP. ADP is converted to ATP by oxidative phosphorylation. Reduction of NDPs forms dNDPs.
  1. Reduction of Ribonucleoside diphosphate to 2’-deoxyribonucleoside diphosphate


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