Synthesis of purines and pyrimidines, De novo synthesis of purines, De novo synthesis of pyrimidines, salvage synthesis of purines, salvage synthesis of pyrimidines

1. Synthesis of purines
and pyrimidines
Anam Sharif
Lecturer (University of Okara)

4. Synthesis of
Purines

6. After 1st step the process require 10 steps. These steps require
glutamine , glycine , aspartate, Bicarbonate HCO3 and formyle
-HC=0 that carries tetrahydrofolate cofactor. The product is IMP
(inosine monophosphate) that is intermediate used for the synthesis
of AMP and GMP
In IMP (inosine monophosphate)
• Two nitrogen N comes from glutamine
• glycine contribute one nitrogen and two carbon
• Aspartate contribute amine group
• Carbon group comes from Bicarbonate
• Two carbons derive from formyle
Aspartate, formate, glutamine, glycine and bicarbonate act as
building blocks for purines

7. Adenine and guanine are the principal purines of both DNA and RNA.

13. Nucleoside and Nucleotides
Nucleoside is a structure formed by the combination of nitrogen base and sugar
where as Nucleotides are phosphoric acid esters of nucleosides.

15. Formation of di and tri phosphate
The nucleoside monophosphates (AMP & GMP)
converted to the corresponding di & triphosphates.
This is achieved by the transfer of phosphate group from
ATP, catalysed by nucleoside monophosphate (NMP)
kinases & nucleoside diphosphate (NDP) kinases.

18. Regulation of Purine nucleotide synthesis
• The intracellular concentration of PRPP regulates purine synthesis.
• This is dependent on the availability of ribose 5-phosphate & the PRPP synthetase.
• If AMP & GMP are available in adequate amounts, their synthesis is turned off at
the amidotransferase reaction.
• Another important stage of regulation is in the conversion of IMP to AMP & GMP.
• AMP inhibits adenylsuccinate synthetase while GMP inhibits IMP dehydrogenase.
• AMP & GMP control their respective synthesis from IMP.

19. Synthesis of
Pyrimidines

20. • Pyrimidines that occur in DNA are cytosine
and thymine. Cytosine and uracil are the
pyrimidines in RNA.
• The biosynthesis of pyrimidine is a simpler
process than the purines.
• In the de novo synthesis of Pyrimidines, the
ring is synthesized first and then it is attached
to a ribose-phosphate to for a pyrimidine
nucleotide.
• Pyrimidine rings are assembled from
bicarbonate, aspartate, and Ammonia.

21. • Pyramidines synthesis is a de-novo synthesis pathway
involving six steps reactions. This pathway results in
the synthesis of Uridine Mono phosphate.
• This process require amino acids to form the UMP we
need amino acids
a) Amine group derive from glutamine
b) Carbon group comes from Bicarbonate
c) 3 carbon and 1 nitrogen derived from aspartate
• UMP is act as a precursor of CTP and dTTP.

26.  Uracil + ribose-1-phosphate ↔ uridine + Pi
uridine + ATP ↔ UMP + ADP
 thymine + deoxyribose-1-phosphate ↔ thymidine + Pi
thymidine + ATP → dTMP + ADP