Pyrimidines are aromatic heterocycles crucial in nucleic acids, synthesized through simpler de novo and salvage pathways. The de novo pathway involves six enzymatic reactions leading to the formation of uridine-5-monophosphate (UMP), which further converts into other pyrimidine nucleotides. Pyrimidines play essential roles as building blocks of nucleic acids and have applications in antibiotics and antiviral treatments.
BIOSYNTHESIS OF PYRIMIDINES
INTRODUCTION:
• Pyrimidine is an aromatic heterocyclic organic compound. It has two nitrogen atoms at
position 1 and 3 in the ring.
• In nuclei acids, three types of nucleobases are pyrimidine derivatives –
SOURCE : PRESENTED BY:
PRASHANT VC
DEPT OF ZOOLOGY
GUK
2.
BIOSYNTHESIS :
• Thebiosynthesis of pyrimidines is a simpler process than purines.
• There are two pathways leading to pyrimidine synthesis:
SALVAGE PATHWAY – the synthesis of nucleotides by recycle the free bases or nucleosides
released from nuclei acid breakdown.
DE NOVO PATHWAY – the synthesis of nucleotides begin with their metabolic precursors :
amino acids, ribose-5-phosphate, carbon dioxide and one-carbon units.
• Pyrimidine synthesis is a de novo synthesis pathway involving six steps reactions.
• The six members pyrimidine ring is made first and then attached to ribose-5-
monophosphate.
• This pathway results in the synthesis of Uridine-5-monophosphate (UMP).
• Out of 6 enzymes involved in this pathway, 5 are present in the cytosol and 1 is present on
the outer surface of inner mitochondrial membrane.
3.
DE NOVO SYNTHESISOF UMP :
STEP 1 : synthesis of
carbamoyl phosphate
STEP 2 : synthesis of
carbamoyl aspartate
STEP 3 : ring closure and
dihydroorotate formation
STEP 4 : oxidation of
dihydroorotate
STEP 5 : acquisition of the
ribose phosphate moiety
STEP 6 : decarboxylation to
form UMP
4.
SYNTHESIS OF OTHERPYRIMIDINE
NUCLEOTIDES :
The UMP thus formed is converted to UDP
by an ATP-dependent kinas reaction.
UDP serves as a precursor for the synthesis
of dUMP, dTMP, UTP AND CTP.
Ribonucleotide reductase converts UDP to
dUDP, by a thioredoxin-dependent
reaction.
From N^5 ,N^10-methylene
tetrahydrofolate methyl group is
transferred to form deoxythymidine
monophosphate.
UDP produce UTP and then cytidine
triphosphate is synthesized from UTP by
amination.
5.
IMPORTANCE:
• Essential buildingblocks of nucleic acids
• Biologically very important heterocycles
• Used in anti-biotics , used as anti-bacterical and anti-fungal also
• Derivative of pyrimidine also possess good anti-viral properties
REFERENCE :
• Lehninger_Principles_of_BIOCHEMISTRY 6th edition
• Textbook of biochemistry: U. Satyanarayana U. Chakrapani
• www.ncbi.nlm.nih.gov
• www.boundless.com/textbooks