De novo and salvage pathway of purines

de novo and salvage pathway of purines

1. DEPARTMENT OF FORENSIC BIOLOGY
ACADEMIC SEMINAR ON
‘DE NOVO AND SALVAGE PATHWAY OF PURINES’
PRESENTED BY-
JAYATI MISHRA
UNDER THE GUIDENCE OF:
PRADIP HIRAPUE
ASST PROF. FORENSIC BIOLOGY
Institute Of Forensic Science
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2. CONTENTS J
INTRODUCTION
J
FUNCTION OF NUCLEOTIDES
J
DE NOVO PATHWAY
J
SALVAGE PATHWAY REFERENCES
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J
REFERENCES

3. INTRODUCTION
J
Nucleotides are buildingblocks of nucleic acids.
J
They are non-essential nutrients , because they can be
synthesized in the body.
J
Nucleic acids occur in the nucleoprotein.
J
Nucleic acids are further digested in the small intestine to
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J
Nucleic acids are further digested in the small intestine to generate nucleotides.
J
Nucleotides are absorbed into intestinal mucosa cells ,
where they are degraded to three components : base ,
pentose , phosphate.
Pentose is absorbed but base is degraded and excreted

4. NITROGENEOUS BASE
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5. Structure Of Nucleotide
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6. Functions of Nucleotides
1.
Theyserveasbuildingblocksofnucleicacids.
2.
ATPplaysanimportantroleinenergytransformation.
3.
ATP,ADP,andAMPmayfunctionasallostericregulators
and participate in regulation of many metabolic path-
ways
.
ATP
involves
in
covalent
modification
of
enzymes
.
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ways
.
ATP
involves
in
covalent
modification
of
enzymes
.
4.
CAMPandcGMParesecondmessengers.

7. Purine Nucleotide Metabolism
Anabolism
J
There are two pathways of synthesis of purine nucleotides :
1.the De Novo synthesis pathway and the
2.Salvage pathway.
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J
The former is the main synthesis pathway of nucleotides ,
the latter is important one in brain and bone marrow. J
The de novo synthesis of purine nucleotide means using
phosphoribose , amino acids , one carbon units and CO2
as raw materials to synthesize purine nucleotide from the
beginning.

8. De novo pathway
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9. Contd
.
J
The pathway can be divided into two stages.
J
Stage one : formation of inosine monophosphate ( IM P )
J
Stage two : conversion of IMP to either AMP or GMP
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J
Stage One
J
PRPP synthetase
J
R5P + ATP--------------------------- JPRPP + AMP
J
amidotransferase
J
PRPP + Gln--------------------------- JPRA + Glu

10. Contnd.
Stage Two
J
The conversion of IMP either to AMP or GMP requires
two reactions.
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GTP,Mg++,adenylosuccinate synthase
J
IMP + Asp------------------------------- Jadenylosuccinate
adenylosuccinate lyase
J
Adenylosuccinate----------------------- JAMP + fumarate

11. Contd.
IMP dehydrogenase
J
IMP + H2O + NAD+---------------JXMP + NADH + H+
ATP, Mg++, GMP synthase
J
XMP + Gln------------------------------------ JGMP + Glu
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J
Nucleoside triphosphates are the most common nucleotide
used in metabolism.
J
ATP is synthesized from ADP and Pi via oxidative.
phosphorylation or substrate level phosphorylation.

12. Contd.
J
ADP is synthesized from AMP in a reaction catalyzed by
adenylate kinase.
AMP + ATP------------------------- J2ADP
J
Other NTPs are also synthesized in ATP
-
requiring reactions
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J
Other NTPs are also synthesized in ATP
-
requiring reactions
catalyzed by corresponding NMP kinases.
NMP + ATP------------------------- JNDP + ADP
J
NDP kinase catalyzes the formation of NTP.
NDP + ATP------------------------- JNTP + ADP

13. Regulation of de novo Pathway
J
PRPP activates amidotransferase.
J
IMP , AMP and GMP inhibit PRPP synthetase.
J
AMP inhibits conversion of IMP to GMP and GMP inhib its
conversion of IMP to AMP.
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conversion of IMP to AMP.
J
ATP stimulates conversion of IMP to GMP and GTP sti mulates
conversion of IMP to AMP.
J
That ensures a balanced synthesis of both families of purine
nucleotides.

14. Salvage Pathway of Purine Nucleotides
J
Many cells have mechanisms to retrieve purine bases and
purine nucleosides. They are used to synthesize purine
nucleotides.
This is the salvage pathway.
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15. Contd.
J
From Base to Nucleotides
APRT
J
A + PRPP-------------------------------- JAMP + ppi
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HGPRT
J
H + PRPP-------------------------------- JIMP + ppi
HGPRT
J
G + PRPP-------------------------------- JGMP + ppi

16. Contnd.
J
From Nucleoside to Nucleotide
AR kinase
J
AR + ATP-------------------------------- JAMP + ADP
J
In comparison to de novo pathway, salvage pathway
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J
In comparison to de novo pathway, salvage pathway is energy-saving.
J
In brain and bone marrow tissues salvage pathway is the
only pathway of nucleotide synthesis.
J
Deficiency of HGPRT causes Lesch Nyhan syndrome

17. Antimetabolites of Purine Nucleotides J
Antimetabolites of purine nucleotides are analogues of
purine, amino acids or folic acid.
J
They either act as competitive inhibitors of enzymes in
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J
They either act as competitive inhibitors of enzymes in purine nucleotides synthesis or can be incorporated into
purine nucleotides.
J
Thus they block purine nucleotides synthesis or interfere in
nucleic acids synthesis.

18. Contd
.
J
6-MP and 6-MG are purine analogues
.
J
6-MP nucleotide is structurally similar to IMP and inhibits conversion of IMP to AMP and GMP.
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conversion of IMP to AMP and GMP.
J
It also blocks synthesis of PRA from PRPP ,, synthesis of
GMP and IMP from G and H respectively.

19. Contd
.
J
Azaserine and diazonorleucine are amino acid
analogues.
J
They are analogues of Gln and interfere with Gln in
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J
They are analogues of Gln and interfere with Gln in purine nucleotide de novo synthesis.
J

20. Catabolism of Purine Nucleotide
J
AMP undergoes hydrolysis and deamination, the A residue
is converted to H. H is oxidized , yielding X and X is
oxidized ,yielding uric acid.
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J
GMP is hydrolyzed and G is released. G is converted to X
and X is oxidized yielding uric acid.

21. Contd
.
J
In the human body the purine ring can not be degrad ed.
J
Uric acid contains the purine ring and is less solu ble in
water.
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water.
J
Certain genetic defects in purine metabolism can ca use
high blood levels of uric acid and results in a dis ease
known as gout.

22. REFERENCES
J
Mc Curry, JE; Begley, TP (2005). The organic chemistry of 
biological pathways . Roberts & Company.
J
Alberts B, Johnson A, Lewis J, Raff M, Roberts K &  Wlater P 
(2002).Molecular Biology of the Cell (4th ed.). Garland Science
J
David.L.Nelson,Michael.M.Cox …,,  
Lehninger Principles Of 
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J
David.L.Nelson,Michael.M.Cox …,,  
Lehninger Principles Of 
Biochemistry.4
th
ed.

23. THANK YOU
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