metabolism of nucleotide

1. By,
Pillai Aswathy viswanath
PG 1 Botany
St. thomas college

2.  Nucleotides are organic molecules that serve as
the sub units of nucleic acid like DNA and RNA
 Building blocks of nucleic acid.
 Nucleotides are composed of a sugar molecule a
phosphate unit, and a nitrogenous base.
 Nucleotides contain either a purine or
a pyrimidine base.
 They are found everywhere within the cells of
our bodies, including the nucleus and the
cytoplasm.

3.  Nucleotides are the activated precursors of DNA
and RNA.
 ATP, an adenine nucleotide, is a universal
currency of energy in biological systems.
 GTP is an essential carrier of chemical energy.
 Components of the cofactors NAD+, FAD, and
coenzyme A
 nucleotides function as cellular messengers for
communication from the outside to the inside of
the nucleus
 They are activated intermediates in many
biosynthesis

4.  Metabolism, inclusive term for the chemical
reactions by which the cells of an organism
transform energy, maintain their identity, and
reproduce.
 Anabolism and Catabolism
 Anabolism (synthesis) and catabolism
(destruction). Both processes go on
throughout the life of the organism.

5.  Purines and pyrimidines are required
for synthesizing nucleotide
 These molecules can be synthesized
either from denovo or salvaged from
existing bases

6.  de novo pathway (a new):
nucleotides are synthesised from different
small components.
The synthesis of nucleotides begins with their
metabolic precursors: amino acids, ribose-5-
phosphate, CO2, and one-carbon units.
 salvage pathways (to save from loss):
recovery and recycling of
nucleotides obtained in the diet

7.  Basic pathway for biosynthesis of purine
nucleotides
 occurs primarily in the liver
 This pathway operates in cytoplasm.
 Requires 10 steps overall
 Purine ring is build up on a (R-5-P) as the
starting material step by step.

8. John Buchanan (1948) "traced" the sources of
all nine atoms of purine ring
 N-1: aspartic acid
 N-3, N-9: glutamine
 C-4, C-5, N-7: glycine
 C-6: CO2
 C-2, C-8: one carbon units

9. N10-Formyltetrahydrofolate
N10-Formyltetrahydrofolate
1. Element sources of purine bases
Formation of purine ring

10. OH
1
ATP
AMP
1
Preliminary step or step 0:
Step 1:Addition of N9
5-磷酸核糖,PRA
•1 N +R-5-P=PRA
PRPP Donor of
R-5-P
Gln:PRPP amidotransferase

11. 酸
2
Step 2: in corporation of C4, C5, and N7
glycinamide synthetase

12. •Step 3: addition of C8
GAR transformylase

13. 4
Step 4: addition of N3

14. 5
苷酸
•Step 5: closing of the ring

15. Carboxyaminoimidazole
ribonucleotide (CAIR)
6
Step 6: addition of C6
AIR carboxylase

16. Carboxyaminoimidazole
ribonucleotide (CAIR)
Step 7: addition of N1
SAICAR synthetase

17. Step 8: removal of fumaric acid
adenylosuccinate lyase

18. Step 9: addition of C2
AICAR transformylase

19. Step 10: ring closure to form IMP
• Once formed, IMP is rapidly
converted to AMP and GMP (it does
not accumulate in cells).

20. AMP and GMP are Synthesized from IMP

21.  shorter pathway than for purines
 requires 6 steps (instead of 10 for purine)
 Pyrimidine ring is made first, then attached to
ribose-P (unlike purine biosynthesis)
 only 2 precursors (aspartate and glutamine,
plus HCO3
-) contribute to the 6-membered
ring
 the product is UMP (uridine monophosphate)

22. N3 originally
from glutamine;
C2 from HCO3

23. •Carbamoyl phosphate synthetase(CPS) exists in 2 types:
•CPS-I, a mitochondrial enzyme, is dedicated to the urea cycle and
arginine biosynthesis.
•CPS-II, a cytosolic enzyme, used here. It is the committed step in animals.

24. ATCase: aspartate transcarbamoylase

26. Step 4:
oxidation of
dihydroorotate
to orotate
(a pyrimidine)

27. Step 6: decarboxylation of
OMP

28. UDP
ADP
UTP
ATP ADP
UMP
ATP
kinase kinase
UTP and CTP biosynthesis

29.  Purines built up on ribose
 PRPP synthetase: key step
 First, synthesis IMP
 Pyrimidine rings built, then ribose
added
 CPS-II: key step
 First, synthesis UMP

30.  This pathway ensure the recovery and
recycling of nucleotides from existing
bases
 This pathway is occure where the de
novo pathway is not operating;
 importance in tissue like RBCs and
brain.
 PRPP is the starting material in this
pathway.

31.  During cellular metabolism and during
digestion in animals, nucleic acids are
degraded to mononucleotides,
nucleosides, and free purine bases.
 The free purines are salvaged by 2 different
enzyme:
 APRT (adenine phosphoribosyl transferase) for
adenine.
 HGPRT (hypoxanthine guanine phosphoribosyl
transferase) for guanine or hypoxanthine.

32. N
NN
N
NH2
O
Guanine
N
N N
O
N
Hypoxanthine
O
OHHO
2-O3POH2C
N
N N
O
N
IMP
O
OHHO
2-O3POH2C
N
NN
N
NH2
O
GMP
.
.
Adenine AMP
PRPP PPi
adenine
phosphoribosyl transferase
PRPP PPi
hypoxanthine-guanine
phosphoribosyl transferase
(HGPRT)

33.  Vasudevan DM,Sreekumari S
(2001).Textbook of biochemestry(for medical
students).JAYPEEBROTHERS medical
publishers LTD New Delhi.
 Robert K Murray,Peter A Mayes, Daryle K
Granner,Victor W Rodwell(1990).Harper’s
biochemestry.Lange Medical publications
 www.google.com, wikipedia.org

34. By,Pillai Aswathy Viswanath