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PURINES

BIOCHEMISTRY

mprasadnaidu
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PURINES

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  1. PURINE METABOLISM M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.

  2. Purine ring structure

  3. PRPP : • It is 5- phoshoribosyl – 1- pyrophosphate. • This is the substrate for denovo synthesis and also salvage pathways of bothpurine and pyrimidine synthesis.

  4. Formation of PRPP : It is formed by transfer of pyrophosphate from ATP to carbon 1 of α-D-ribose- 5-P, catalysed by PRPP -synthase.

  5. Addition of N9 – in purine synthesis: Amide group of glutamine is transferred to C1 of PRPP by PRPP glutamylamidotransferase,forming 5-phosphoribosyl -1- amine. It is rate limiting step.

  6. Regulation of purine synthesis: 1.The commited step in denovo synthesis is PRPP glutamyl amidotransferase . AMP and GMP act as allosteric modifiers.

  7. 2.PRPP synthetase is important enzyme that regulates purine synthesis. Inhibited allosterically by feedback effects of PRPP, purine nucleotides AMP , GMP,ADP, GDP.

  8. Salvage pathway of purines – one step synthesis

  9. In denovo synthesis of pyrimidines: Transfer of ribose phosphate: This is transferred from PRPP, forming OMP(orotidylate), catalysed by orotate – phosphoribosyl transferase. PRPP PPI

  10. SALVAGE PATHWAY OF PYRIMIDINE SYNTHESIS Pyrimidine base + PRPP pyrimidine phosphoribosyl transferase Pyrimdine nucleotide + PPi

  11. SALVAGE PATHWAYS

  12. SALVAGE PATHWAY OF PURINE SYNTHESIS: This pathway ensures Recycling of purines by degradation of nucleotides.

  13. 1.The denovo synthesis is expensive. 2. All tissues are not capable of denovo synthesis Eg: RBC , Brain,neutrophils . They lack PRPP amidotransferase.

  14. 3. Nucleotides donot enter cellsdirectly,but converted to nucleosides by cell membrane nucleosidases. 4.After entering into cell ,nucleoside is converted to nucleotide (by kinase)/ or degraded to corresponding base(by nucleoside phosphorylase)

  15. Salvage pathway of purines – one step synthesis

  16. Salvage pathway – two step synthesis Nucleoside phosphorylase – nucleoside kinase

  17. SALVAGE PATHWAY OF PYRIMIDINE SYNTHESIS Pyrimidine base + PRPP pyrimidine phosphoribosyl transferase Pyrimdine nucleotide + PPi

  18. Thank you

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