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
INTRODUCTION
FUNCTION OF NUCLEOTIDES
DE NOVO PATHWAY
SALVAGE PATHWAY
REFERENCES
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3. INTRODUCTION
Nucleotides are building blocks of nucleic acids.
They are non-essential nutrients , because they can be
synthesized in the body.
Nucleic acids occur in the nucleoprotein.
Nucleic acids are further digested in the small intestine to
generate nucleotides.
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
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4. NITROGENEOUS BASE
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5. Structure Of Nucleotide
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6. Functions of Nucleotides
1. They serve as building blocks of nucleic acids.
2. ATP plays an important role in energy transformation.
3. ATP , ADP, and AMP may function as allosteric regulators
and participate in regulation of many metabolic path-ways.
ATP involves in covalent modification of enzymes.
ways. 4. CAMP and cGMP are second messengers.
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7. Purine Nucleotide Metabolism
Anabolism
There are two pathways of synthesis of purine nucleotides :
1.the De Novo synthesis pathway and the
2.Salvage pathway.
The former is the main synthesis pathway of nucleotides ,
the latter is important one in brain and bone marrow.
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.
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8. De novo pathway
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9. Contd.
The pathway can be divided into two stages.
Stage one : formation of inosine monophosphate ( IMP )
Stage two : conversion of IMP to either AMP or GMP
Stage One
PRPP synthetase
R5P + ATP---------------------------PRPP + AMP
amidotransferase
PRPP + Gln---------------------------PRA + Glu
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10. Contnd.
Stage Two
The conversion of IMP either to AMP or GMP requires
two reactions.
GTP,Mg++,adenylosuccinate synthase
IMP + Asp-------------------------------adenylosuccinate
adenylosuccinate lyase
Adenylosuccinate-----------------------AMP + fumarate
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11. Contd.
IMP dehydrogenase
IMP + H2O + NAD+---------------XMP + NADH + H+
ATP, Mg++, GMP synthase
XMP + Gln------------------------------------GMP + Glu
Nucleoside triphosphates are the most common nucleotide
used in metabolism.
ATP is synthesized from ADP and Pi via oxidative.
phosphorylation or substrate level phosphorylation.
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12. Contd.
ADP is synthesized from AMP in a reaction catalyzed by
adenylate kinase.
AMP + ATP------------------------- 2ADP
Other NTPs are also synthesized in ATP-requiring reactions
catalyzed by corresponding NMP kinases.
NMP + ATP-------------------------NDP + ADP
NDP kinase catalyzes the formation of NTP.
NDP + ATP-------------------------NTP + ADP
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13. Regulation of de novo Pathway
PRPP activates amidotransferase.
IMP , AMP and GMP inhibit PRPP synthetase.
AMP inhibits conversion of IMP to GMP and GMP inhibits
conversion of IMP to AMP.
ATP stimulates conversion of IMP to GMP and GTP stimulates
conversion of IMP to AMP.
That ensures a balanced synthesis of both families of purine
nucleotides.
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14. Salvage Pathway of Purine Nucleotides
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.
From Base to Nucleotides
APRT
A + PRPP--------------------------------AMP + ppi
HGPRT
H + PRPP--------------------------------IMP + ppi
HGPRT
G + PRPP--------------------------------GMP + ppi
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16. Contnd.
From Nucleoside to Nucleotide
AR kinase
AR + ATP--------------------------------AMP + ADP
In comparison to de novo pathway, salvage pathway
is energy-saving.
In brain and bone marrow tissues salvage pathway is the
only pathway of nucleotide synthesis.
Deficiency of HGPRT causes Lesch Nyhan syndrome
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17. Antimetabolites of Purine Nucleotides
Antimetabolites of purine nucleotides are analogues of
purine, amino acids or folic acid.
They either act as competitive inhibitors of enzymes in
purine nucleotides synthesis or can be incorporated into
purine nucleotides.
Thus they block purine nucleotides synthesis or interfere in
nucleic acids synthesis.
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18. Contd.
6-MP and 6-MG are purine analogues
.
6-MP nucleotide is structurally similar to IMP and inhibits
conversion of IMP to AMP and GMP.
It also blocks synthesis of PRA from PRPP ,, synthesis of
GMP and IMP from G and H respectively.
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19. Contd.
Azaserine and diazonorleucine are amino acid
analogues.
They are analogues of Gln and interfere with Gln in
purine nucleotide de novo synthesis.
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20. Catabolism of Purine Nucleotide
AMP undergoes hydrolysis and deamination, the A residue
is converted to H. H is oxidized , yielding X and X is
oxidized ,yielding uric acid.
GMP is hydrolyzed and G is released. G is converted to X
and X is oxidized yielding uric acid.
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21. Contd.
In the human body the purine ring can not be degraded.
Uric acid contains the purine ring and is less soluble in
water.
Certain genetic defects in purine metabolism can cause
high blood levels of uric acid and results in a disease
known as gout.
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22. REFERENCES
Mc Curry, JE; Begley, TP (2005). The organic chemistry of
biological pathways. Roberts Company.
Alberts B, Johnson A, Lewis J, Raff M, Roberts K Wlater P
(2002). Molecular Biology of the Cell (4th ed.). Garland Science
David.L.Nelson,Michael.M.Cox …,, Lehninger Principles Of
Biochemistry.4th ed.
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23. THANK YOU
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