Nucleotide Synthesis

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 .