This document provides an overview of nucleotide biosynthesis. It discusses that nucleotides are composed of nitrogenous bases, pentose sugars, and phosphate groups, and are the building blocks of nucleic acids. There are two pathways for nucleotide biosynthesis - de novo synthesis which uses metabolic precursors to build nucleotides from scratch, and salvage pathways which recycle bases and nucleosides from nucleic acid breakdown. Key steps in purine and pyrimidine synthesis are described. Nucleotides have important biological functions as components of nucleic acids, energy carriers, and signaling molecules.

1. BIOSYNTHESIS OF
NUCLEOTIDES
BIOSYNTHESIS OF NUCLEOTIDES
PRESENTED
BY
PRACHEE RAJPUT
(M.Sc ZOOLOGY, 1ST SEM. )
DEPARTMENT OF ZOOLOGY & APPLIED AQUA- CULTURE
BARKATULLAH UNIVERSITY, BHOPAL(M.P)

2. SYNOPSIS
INTRODUCTION
DEFINITION
BIOSYNTHESIS
(a) de-novo pathway
(b) salvage pathway
FUNCTION
CONCLUSION
REFERENCES

3. INTRODUCTION
Nearly all organisms synthesize purines and
pyrimidines de novo (“anew”).
Many organisms also "salvage" purines and
pyrimidines from diet and degradative
pathways.
Ribose generates energy, but purine and
pyrimidine rings do not.
Nucleotide synthesis pathways are good targets
for anti-cancer/antibacterial strategies.

4. Nucleotides
RNA (ribonucleic acid) is a polymer of
ribonucleotides
DNA (deoxyribonucleic acid) is a polymer of
deoxyribonucleotides
Both deoxy- and ribonucleotides contain
Adenine, Guanine and Cytosine
Ribonucleotides contain Uracil
Deoxyribonucleotides contain Thym

5. Nitrogenous Bases
• Planar, aromatic, and heterocyclic
• Derived from purine or pyrimidine
• Numbering of bases is “unprimed”

6. Nucleic Acid Bases
Purines Pyrimidines

7. Sugars
• Pentoses (5-C sugars)
• Numbering of sugars is “primed”

8. DEFINITION
Nucleotides are the units of nucleic acids
and composed of nitrogenous
base,pentose sugar,and phosphate
group.
These are the building blocks of nucleic
acids (DNA and RNA).
2. Involved in energy storage, muscle
3. contraction,
active transport, maintenance of ion
gradients

9. BIOSYNTHESIS
There are two types of pathways lead to
nucleotides: de-novo pathways and the salvage
pathways.
De-novo synthesis of nucleotides begins with
their metabolic precursors: Amino acids,ribise-
5-phosphate,carbon dioxide and ammonia.
Salvage pathways recycle the free bases and
nucleosides released from nucleic acid break
down both types of pathways are important in
cellular metabolism.

10. Two major routes for nucleotide
biosynthesis
dNTPs
dNTPs
Stryer Fig. 25.1

11. Purine Nucleotide Synthesis
OH
H
H
CH2
OH OH
H H
O

O2-
O3P
-D-Ribose-5-Phosphate (R5P)
O
H
H
CH2
OH OH
H H
O 
O2-
O3P
5-Phosphoribosyl--pyrophosphate (PRPP)
P
O
O
O P
O
O
O
ATP
AMP
Ribose
Phosphate
Pyrophosphokinase
H
NH2
H
CH2
OH OH
H H
O

O2-
O3P
-5-Phosphoribosylamine (PRA)
Amidophosphoribosyl
Transferase
Glutamine
+ H2O
Glutamate
+ PPi
H
NH
H
CH2
OH OH
H H
O
O2-
O3P
CO
H2C NH2
Glycinamide Ribotide (GAR)
GAR Synthetase
Glycine
+ ATP
ADP
+ Pi
H2C
C
NH
O
CH
H
N
O
Ribose-5-Phosphate
Formylglycinamide ribotide (FGAR)
H2C
C
NH
O
CH
H
N
HN
Ribose-5-Phosphate
Formylglycinamidine ribotide (FGAM)
THFN10
-Formyl-THF
GAR Transformylase
ATP +
Glutamine +
H2O
ADP +
Glutamate + Pi
FGAM
Synthetase
HC
C
N
CH
N
H2N
Ribose-5-Phosphate
4
5
5-Aminoimidazole Ribotide (AIR)
ATP
ADP + Pi
AIR
Synthetase
C
C
N
CH
N
H2N
OOC
Ribose-5-Phosphate
4
5
Carboxyamidoimidazole Ribotide (CAIR)
ATP
+HCO3
ADP + Pi
AIR
Car boxylase
Aspartate
+ ATP
ADP
+ Pi
SAICAR Synthetase
Adenylosuccinate
Lyase
Fumarate
C
C
N
CH
N
NH
Ribose-5-Phosphate
4
5
5-Formaminoimidazole-4-carboxamide
ribotide (FAICAR)
C
H2N
O
C
H
O
C
C
N
CH
N
H2N
Ribose-5-Phosphate
4
5
5-Aminoimidazole-4-carboxamide
ribotide (AICAR)
C
H2N
O
C
C
N
CH
N
H2N
C
N
H
O
HC
COO
CH2
COO
Ribose-5-Phosphate
4
5
5-Aminoimidazole-4-(N-succinylocarboxamide)
ribotide (SAICAR)
THF
AICAR
Transformylase
N10
-Formyl-
THF
Inosine Monophosphate (IMP)
HN
HC
N
C
C
C
N
CH
N
O
4
5
HH
CH2
OH OH
H H
OO2-
O3P
IMP
Cyclohydrolase
H2O

12. Purine Salvage Pathways
Nucleic acid turnover (synthesis and degradation) is an
ongoing process in most cells.
Salvage pathways collect hypoxanthine and guanine
and recombine them with PRPP to form nucleotides in
the HGPRT reaction.
(Hypoxanthine-guanine phosphoribosyltranferase).
In L-N, purine synthesis is increased 200-fold and uric
acid is elevated in blood.
This increase may be due to PRPP feed-forward
activation of de novo pathways.

13. HGPRT Converts Bases Back to Nucleotides
Using PRPP
Salvage pathways are very useful because of the high
energy cost for denovo synthesis of nitrogen bases. The
salvage pathway for adenine recovery
(adenine phosphoribosyltranferase) is not shown.

14. Some Commonly Used Enzymes
• Nucleotidases cleave Pi from a nucleotide.
• Nucleosidases cleave the base from a nucleoside.
• Nucleoside phosphorylase cleaves the base from a nucleoside
using Pi.
• Nucleoside kinase adds phosphate to a nucleoside.

15. 2 ATP + HCO3
-
+ Glutamine + H2O
CO
O PO3
-2
NH2
Carbamoyl Phosphate
NH2
C
N
H
CH
CH2
C
COO
O
HO
O
Carbamoyl Aspartate
HN
C
N
H
CH
CH2
C
COO
O
O
Dihydroorotate
HN
C
N
H
C
CH
C
COO
O
O
Orotate
HN
C
N
C
CH
C
COO
O
O
HH
CH2
OH OH
H H
O
O2-
O3P

Orotidine-5'-monophosphate
(OMP)
HN
C
N
CH
CH
C
O
O
HH
CH2
OH OH
H H
O
O2-
O3P

Uridine Monophosphate
(UMP)
2 ADP +
Glutamate +
Pi
Carbamoyl
Phosphate
Synthetase II
Aspartate
Transcarbamoylase
(ATCase)
Aspartate
Pi
H2O
Dihydroorotase
Quinone
Reduced
Quinone
Dihydroorotate
Dehydrogenase
PRPP PPi
Orotate Phosphoribosyl
Transferase
CO2
OMP
Decarboxylase
Pyrimidine Synthesis

16. Pyrimidine Synthesis
In contrast to purines, pyrimidines are not
synthesized as nucleotides.
Rather, the pyrimidine ring is completed before a
ribose-5-P is added.
Carbamoyl-phosphate and aspartate are the
precursors of the six atoms of the pyrimidine ring.
Mammals have two enzymes for carbamoyl
phosphate synthesis – carbamoyl phosphate for
pyrimidine synthesis is formed by carbamoyl
phosphate synthetase II (CPS-II), a cyt

17. Biological functions of
nucleotides
Building blocks of nucleic acids (DNA and RNA).
2. Involved in energy storage, muscle contraction,
active transport, maintenance of ion gradients.
3. Activated intermediates in biosynthesis
(e.g. UDP-glucose, S-adenosylmethionine).
4. Components of coenzymes (NAD+, NADP+, FAD,
FMN, and CoA)
5. Metabolic regulators:
a. Second messengers (cAMP, cGMP)
b. Phosphate donors in signal transduction (ATP)
c. Regulation of some enzymes via adenylation
and uridylylation

18. conclusion
From the above discussion it has been concluded
nucleotides are the building blocks of RNA and
DNA, This means that nucleotides act as a
monomers units large no. of monomers units
polymerize to form a polymer (‘RNA’ and ‘DNA’)
RNA and DNA are the genetic material that
inherits from one generation to other i.e. (parents
to offsprings).

19. REFERENCES
LEHNINGER PRINCIPAL OF BIOCHEMISTRY BY
NELSON AND COX
BIOCHEMISTRY BY SATYANARAYANA AND
CHAKRAPANI

20. THANKS