biochemistry

1. PYRIMIDINE
BIOSYNTHESIS &
DEGRADATION
SUBHANANTHINI JEYAMURUGAN,
18PY17, M.SC., MICROBIOLOGY.
AYYA NADAR JANAKI AMMAL COLLEGE, SIVAKASI.

2. PYRIMIDINE
Its an aromatic heterocyclic, organic compound. It has the nitrogen atoms at the
position of 1 and 3 in the ring. The atoms derived from CO2 , NH3 and aspartate.
Formula - C4H4N2
Other names – 1, 3- Diazine
m - diazine

3. Structure

4. …
 It is similar to purine synthesis.
Here the ring is first synthesized and attached to the
ribose po4. they are assembled by aspartate,
bicarbonate and NH3.
 First observed in mutants of bread
mold Neurospora crassa.

5. about…
Biosynthesis of pyrimidines is simple than that of purines.
Unlike purine synthesis, pyrimidines are synthesized as
bases and latter it is added to ribose sugar, i.e., the ring is
completed before being it is linked to ribose-5-phosphate.

6. Synthesis of Pyrimidine Nucleotides
Precursors
◦ Amino acids (Aspartate, Glutamine)
◦ CO2 (from HCO3
-)
◦ Ribose-5-phosphate (HMP shunt & nucleosides)
Enzymes
Coenzymes and Cofactors
◦ NAD+, NADPH, Mg++
ATPs
◦ Energy
◦ PRPP formation

7. Pyrimidine metabolism
Sources of carbon and nitrogen atoms in pyrimidine ring:
7

8. De novo synthesis of pyrimidine
nucleotides - Overview

10. 1: Formation of carbamoyl phosphate
Starting materials for pyrimidine biosynthesis includes bicarbonate, amine from glutamine, and
phosphate from ATP to form carbamoyl phosphate.
The reaction is catalyzed by the cytosolic enzyme carbamoyl phosphate synthetase II (CPS II)
and is the committed step in the mammalian pathway.

12. 2 and 3: Formation of carbamoyl aspartate and
dihyroorotate
• Carbamoyl phosphate condenses with aspartate to form
carbamoyl aspartate.
• Then, dihydroorotate, a closed 6-membered ring structure
is formed by the loss of H2O.
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13. 4 to 6: Formation of UMP, UDP, and UTP
 Dihydroorotate is oxidized to orotic acid, which in turn combined with PRPP to form
orotidine mono-phosphate (OMP).
 OMP is decarboxylated to form uridine monophosphate (UMP)
 UDP is formed from UMP by phosphorylation, catalyzed by a specific nucleoside
monophosphate kinase, UMP kinase
 UDP is converted to UTP by another phosphorylation step catalyzed by nucleoside
diphosphate kinase, an enzyme with broad specificity for nucleoside diphosphates
dihydroorotate
NAD+ NADH+/H+
Orotic acid
PRPP Ppi
orotidine
mono-phosphate (OMP)
OMP
CO2
UMP UDP UTP
ATP ADP ATP ADP
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14. 7. Formation of CTP
UTP CTP
• CTP is formed from UTP
• An amino group from glutamine replaces the keto group in uridine triphosphate (UTP)
to form cytidine triphosphate (CTP).
• Note that: UMP does not form CMP, nor does UDP form CDP. UMP and UDP have to
be converted to UTP first.
glutamine glutamate
ATP ADP + Pi
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16. Synthesis of UTP from UMP
• UMP is converted to UTP in two step
kinase reaction with 2 molecules of ATP
UMP + ATP ⇌ UDP + ADP
UDP + ATP ⇌ UTP + ADP
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19. Thank you