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Purine

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Title: Purine


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 both purine and
    pyrimidine synthesis.

4
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.
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
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10
In denovo synthesis of pyrimidines Transfer of
ribose phosphate This is transferred from
PRPP, forming OMP(orotidylate), catalysed by
orotate phosphoribosyl transferase.
PRPP PPI
11
SALVAGE PATHWAY OF PYRIMIDINE SYNTHESIS
Pyrimidine base PRPP
pyrimidine
phosphoribosyl
transferase
Pyrimdine nucleotide PPi
12
SALVAGE PATHWAYS
13
SALVAGE PATHWAY OF PURINE SYNTHESIS This
pathway ensures Recycling of purines by
degradation of nucleotides.
14
1.The denovo synthesis is expensive. 2. All
tissues are not capable of denovo synthesis Eg
RBC , Brain,neutrophils . They lack PRPP
amidotransferase.
15
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)
16
Salvage pathway of purines one step synthesis
17
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18
Salvage pathway two step synthesis Nucleoside
phosphorylase nucleoside kinase
19
SALVAGE PATHWAY OF PYRIMIDINE SYNTHESIS
Pyrimidine base PRPP
pyrimidine
phosphoribosyl
transferase
Pyrimdine nucleotide PPi
20
Thank you
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