This presentation is based on the metabolic pathways involved in the bio-synthesis of nucleotides- pyrimidine and purine. It includes various stages involves in their synthesis or formation.

1. NUCLEOTIDE
SYNTHESIS
Submitted by :Sameeha Jain
Bsc. Sem -2

2. What is a nucleotide
Any of several compounds that consist of a ribose or
deoxyribose sugar joined to a purine or pyrimidine
base and to a phosphate group and that are the
basic structural units of nucleic acids (such as RNA
and DNA) is nucleotide.

3. PURINE
• Purine is a heterocyclic
aromatic organic
compound composed of a
pyrimidine ring fused with
imidazole ring.
• It consists of two hydrogen-
carbon rings and four
nitrogen atoms.
• The melting point of purine
is 214 °C .
• Catabolism results in the
production of uric acid
PYRIMIDINE
• Pyrimidine is a heterocyclic
aromatic organic compound
that is composed of carbon
and hydrogen.
• It consists of one hydrogen-
carbon ring and two
nitrogen atoms.
• The melting point of
pyrimidine is 20-22 °C.
• Catabolism produces carbon
dioxide, beta-amino acids
and ammonia.

4. Purines and Pyrimidine are
divided into :
Purine
Adenine
Guanine
Pyrimidine
Thymine
Cytosine
Uracil

5. Structures of Purine and Pyrimidine

6. PATHWAYS FOR
BIOSYNTHESIS
• De – novo synthesis : A biochemical pathway
where nucleotides are synthesized new from
simple precursor molecule.
• Salvage Pathway : A salvage pathway is a
pathway in which a biological product is
produced from intermediates in the degradative
pathway of its own or a similar substance used
to recover bases and nucleoside formed during
the degradation of RNA & DNA.

8. SYNTHESIS OF
PURINE
• Purine bases are not synthesized as such,
but they are formed as ribonucleotides.
• The purines are built upon a pre-existing ribose
5-phosphate.
• Liver is the major site for purine nucleotide
synthesis
• Erythrocytes, polymorphonuclear leukocytes and
brain cannot produce purines

9. Continued…
• Purine can be synthesized by De novo
pathway (new synthesis from amphibolic
intermediates) & Salvage pathway (by
phosphoribosylation of free purine bases an
by phosphorylation of purine nucleotides).
• In de novo synthesis , purine nucleotides are
synthesized not the free purine bases.

12. Synthesis of AMP & GMP from IMP
• Synthesis of AMP :
• Ionosine monophosphate
(IMP) is the immediate
precursor for the formation of
AMP & GMP.
• Aspartate condenses with IMP
in the presence of GTP to
produce adenyl succinate
which on cleavage forms
AMP
• Synthesis of GMP :
• IMP undergoes NAD+
dependent dehyrogenation
to form xanthine
monophosphate (XMP).
• Glutamine then transfers
amide nitrogen to
xanthanosine
monophosphate (XMP) to
produce GMP.

14. Salvage Pathway for Purine Synthesis
• The free purines (adenine, guanine and
hypoxanthine) are formed in the normal
turnover of nucleic acids (particularly RNA), and
also obtained from the dietary sources.
• The purines can be directly converted to the
corresponding nucleotides, and this process is
known as 'salvage pathway' .

15. Salvage Pathway for Purine Synthesis

16. SYNTHESIS OF
PYRIMIDINE
• Pyrimidine are not synthesized as
nucleotides, rather the pyrimidine ring is
completed before a ribose-5-P is added.
• Carbonyl – phosphate and aspartate are the
precursors of the six atoms of the pyrimidine
ring.

17. Salient features of Pyrimidine
synthesis
• Glutamine transfers its amido nitrogen to CO2 to produce
carbamoyl phosphate. This reaction is ATP-dependent and
is catalysed by cytosomal enzyme carbamoyl phosphate
synthetase ll (CPS Il).
• Carbamoyl phosphate condenses with aspartate to form
carbamoyl aspartate. This reaction is catalysed by aspartate
transcarbamoylase.
• The next step in pyrimidine synthesis is an NAD+ dependent
dehydrogenation, leading to the formation of orotate.

18. Salient features of Pyrimidine
synthesis
• Ribose 5-phosphate is now added to orotate to produce
orotidine monophosphate (OMP).
• OMP undergoes decarboxylation to uridine mono-
phosphate (UMP).
• By an ATP-dependent kinase reaction, UMP is
converted to UDP which serves as a precursor for the
synthesis .
• UDP undergoes an ATP-dependent kinase reaction to
produce UTP.
• Cytidine triphosphate (CTP) is synthesized from UTP by
amination .