Purine

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PURINE METABOLISM

• M.Prasad Naidu
• MSc Medical Biochemistry, Ph.D,.

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Purine ring structure
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• PRPP
• It is 5- phoshoribosyl 1- pyrophosphate.
• This is the substrate for denovo synthesis and
  also salvage pathways of both purine and
  pyrimidine synthesis.

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Formation of PRPP It is formed by transfer of
pyrophosphate from ATP to carbon 1 of
a-D-ribose- 5-P, catalysed by PRPP -synthase.
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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.
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Regulation of purine synthesis 1.The commited
step in denovo synthesis is PRPP glutamyl
amidotransferase . AMP and GMP act as
allosteric modifiers.
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2.PRPP synthetase is important enzyme that
regulates purine synthesis. Inhibited
allosterically by feedback effects of
PRPP, purine nucleotides AMP , GMP,ADP, GDP.
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Salvage pathway of purines one step synthesis
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In denovo synthesis of pyrimidines Transfer of
ribose phosphate This is transferred from
PRPP, forming OMP(orotidylate), catalysed by
orotate phosphoribosyl transferase.
PRPP PPI
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SALVAGE PATHWAY OF PYRIMIDINE SYNTHESIS
Pyrimidine base PRPP
pyrimidine
phosphoribosyl
transferase
Pyrimdine nucleotide PPi
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SALVAGE PATHWAYS
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SALVAGE PATHWAY OF PURINE SYNTHESIS This
pathway ensures Recycling of purines by
degradation of nucleotides.
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1.The denovo synthesis is expensive. 2. All
tissues are not capable of denovo synthesis Eg
RBC , Brain,neutrophils . They lack PRPP
amidotransferase.
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3. Nucleotides donot enter cells directly,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)
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Salvage pathway of purines one step synthesis
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Salvage pathway two step synthesis Nucleoside
phosphorylase nucleoside kinase
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SALVAGE PATHWAY OF PYRIMIDINE SYNTHESIS
Pyrimidine base PRPP
pyrimidine
phosphoribosyl
transferase
Pyrimdine nucleotide PPi
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