1. Pyrimidine nucleotides are synthesized through a simpler process than purines, using aspartate, glutamine and CO2 to form the pyrimidine ring. 2. The ring is first synthesized and then attached to ribose-5-phosphate, unlike purines which are built upon pre-existing ribose-5-phosphate. 3. Uridine monophosphate (UMP) is the first true pyrimidine ribonucleotide formed through a series of reactions, and is later phosphorylated to form other pyrimidine nucleotides.

1. METABOLISM OF
PYRIMIDINE
NUCLEOTIDES
DR BAKHTAWAR
FAROOQ MPHILL
BIOCHEMISTRY NISHTER

2. PYRIMIDINE
METABOLISM

4. Pyrimidine is a heterocyclic
ring.
Pyrimidine is first synthesized .
Later, it isattached to ribose -5

7. BIOSYNTHESIS OF PYRIMIDINE
RIBONUCLEOTIDES
The synthesis of pyrimidines is a much simpler
process compared to that of purines.
aspartate, gutamine and CO2 contribute to
atoms in the formation of pyrimidine ring.
Pyrimidine ring is first synthesized and then
attached to ribose 5-phosphate.
this is in contrast to purine nucleotide synthesis
where in purine ring is built upon a pre-existing
ribose5-phosphate.

9. 1.Formation of carbomyl phosphate:
Carbomyl phosphate is formed from ATP,
GLUTAMINE
and CO2.
The reaction is catalysed by CPS –II.

10. Differences between CPSI and
CPSII :
CPS I
Mitochondri
a Urea
NAG
Ammonia
--------
CPS II
Cytoplas
m
Pyrimidin
e
------
Glutamin
• SITE
• Pathway of
• Positive
Effector
• Source for N
• Inhibitor

11. 2. Condensation :
Carbomyl phosphate condenses with
aspartate to from carbomylaspartate,
cataylsed by aspartate- transcarbomylase.
Carbomyl phosphate +

12. 3. Ring closure:
This occurs via loss of water. This reaction is
catalysed by dihydroorotase, forming
dihydroorotic acid.

13. 4. Dehydrogenation :
Removal of hydrogen atoms from C5 and C6
, by
dihydroorotate
dehydrogenase.(mitochondrial).

14. 5.Transfer of ribose phosphate : This is
transferred from PRPP, forming
OMP(orotidylate),
catalysed by orotate – phosphoribosyl
transferase.
PRP
P
PP
I

15. 6.Decarboxylati
on:
OMP is decarboxylated forming UMP.
UMP is the first true pyrimidine
ribonucleotide.
co
2

16. 7. Phosphorylation of UMP forms UDP and UTP
, with help of ATP.

17. 8.Formation of CTP :
UTP is aminated by glutamine and ATP, catalysed
by CTP synthase.

18. 9.Reduction of ribonucleoside
diphosphates to their corresponding
dNDP’s .

19. 10.Formation of TMP from UDP:
dUMP is substrate for TMP
synthesis. dUDP is
dephosphorylated to d UMP.

20. 11. Methylation of
dUMP:
This occurs at C5 by N5,N10methyleneTHF,
forming TMP.
This reaction is catalysed by Thymidylate
synthase.

23. Salvage pathway
The pyrimidines (like purines) can also serve as
precursors in the salvage pathway to be converted
to the respective nucleotides.
This reaction is catalysed by pyrimidine
phospshoribosyl transferase which utilizes PRPP
as the source of ribose 5- phosphate.

24. SALVAGE PATHWAY OF PYRIMIDINE
SYNTHESIS
Pyrimidine base + PRPP
pyrimidine
phosphoribosyl
transferase
Pyrimdine nucleotide + PPi

25. Regulation of pyrimidine synthesis:
•CPSII,aspartate transcarbomylase
and dihydrooratase are present as
multienzymecomplex.
•Orotate phosphoribosyl transferase and
OMP – decarboxylase are present as single
functional enzyme. Due to clustering of
these enzymes , the
synthesis is well coordinated.

26. • (CPSII and aspartate transcarbomylase)
And (OPRTransferase and OMP-
decarboxylase) are sensitive to allosteric
regulation.
• CPSII is main regulatory enzyme in
mammalian cells.
• CPS II - inhibited by UTP .
- activated by PRPP
• Aspartate transcarbomylase :
main regulatory enzyme in prokaryotes.
- inhibited by CTP ;activated by ATP

27. •Requirement of ATP for CTP synthesis and
stimulatory effect of GTP on CTP synthase ensures
a balanced synthesis of purines and pyrimidines.

28. Degradation of pyrimidine nucleotides
The pyrimidine nucleotides undergo similar reactions
(dephosphorylation, deamination and cleavage of
glycosidic bond) like that of purine nucleotides to
liberate the nitrogenous bases cytosine, uracil and
thymine.
The bases are then degraded to highlyl soluble
products
β-alanine and β-aminoisobutyrate.
These are the amino acid which undergo
transamination and other reactions to finally produce

30. Disorders of pyrimidine
metabolism: 1.OROTIC
ACIDURIA:
Orotic aciduria type I – deficiency of
Orotatephosphoribosyl transferase and
OMP – decarboxylase.
Orotic aciduria type II :
Rare, deficeincy of ONLY OMP
decarboxylase. Both types are inherited as

31. Features :
•Due to lack of feedback inhibition orotic
acid production is excessive.(UMP
inhibits OMP decarboxylase)
• Rapidly growing cells are affected – anemia
• Retarded growth
•Crystals excreted in urine causing
urinary obstruction.
•Both types respond to uridine , as it is
converted to UTP . This acts as feed back

33. Other causes of orotic aciduria:
1. Deficeincy of liver mitochondrial
ornthine – trancarbomylase (X-
linked).
under utilised substrate carbomyl phosphate
enters cytosol
Stimulates pyrimidine nucleotide
biosynthesis Leading to orotic aciduria

34. 2. Drugs may precipitate orotic aciduria:
a)ALLOPURINOL , a purine analog is a
substrate for Orotate phosphoribosyl
transferase.
It competes for phosphoribosylation with
natural substrate, orotic aicd.
The resulting nucleotide product
inhibits OMP DECARBOXYLASE

35. Reye’s syndrome:
This is considered as a secondary orotic aciduria.
It is believed that a defect in ornithine
trascarbamoylase (or urea cycle ) causes the
accumulation of carbamoyl phosphate.
This is then diverted for the increased synthesis and
excretion of orotic acid.

36. THANK
YOU