Biosynthesis of Pyrimidine

Biosynthesis of Pyrimidine

Biosynthesis of Pyrimidine


       At the end of this lecture, student will be able to

      Explain biochemical reactions of pyrimidine nucleotide biosynthesis

      Discuss the degradation of pyrimidine nucleotides

      Explain the disorders of pyrimidine metabolism

Biosynthesis of pyrimidine nucleotide

       Synthesis of pyrimidine is simpler process then purine

       Aspartate, Glutamine and CO2 contribute the formation of pyrimidine ring

       Here, pyrimidine ring is synthesized and then attached to ribose-5-phosphate

Biosynthesis of Pyrimidine

1. Glutamine transfer the amino nitrogen to co2 to produce carbamoyl phosphate in presence of carbamoyl phosphate synthase-II by utilizing  2 ATP and 1 molecule of H2O

2. Carbmoyl phosphate condenses with aspartate to form carbamoyl aspartate in presence of Aspartate trans carbamoylase

3. Dihydroorotase catalyse the pyrimidine ring to close with a loss of H2O  to form dihydroorotate

4. NAD+ dependent dihydroorotate dehydrogenase convert dihydrooratate to form rotate

5. Ribose-5-phosphate is added to orotate to produce orotidine monophosphate (OMP)

6. OMP undergoes decarboxylation by OMP decarboxylase to form Uridine monophosphate by releasing CO2

7. UMP converts to UDP and finally to UTP by enzyme kinase which serves as a precursor for synthesis of dUMP, dTMP, UTP & CTP

Degradation of Pyrimidine nucleotides

       Pyrimidine undergoes similar reaction

       I.e. dephosphorylation, deamination and cleavage of glycosidic bond and liberate (cytosine, uracil & thymine)

       These bases are then degraded to high soluble product, β-alanine & β– aminoisobutyrate

       These are amino acid which undergoes transamination and other reaction to finally produce acetyl-CoA & succinyl-CoA

       These compounds gets metabolise and excreted through urine

Disorders of pyrimidine metabolism

       Orotic aciduria

Metabolic disorder characterised by excretion of orotic acid in urine, which leads to severe anaemia and retarded growth.

Due to deficiency of enzyme orotate phosphoribosyl transferase and OMP decarboxylase

       Reye’s syndrome

Due to defect in ornithine transcarbamoylase which led to accumulation of carbamoyl phosphate and cause increase synthesis & excretion of orotic acid


1. Aspartate+ Glutamine + Co2 contribute for pyrimidine ring

2. Proceeds only in a cytoplasm of cells

3. Degradation of pyrimidine nucleotides occurs by dephosphorylation, deamination and cleavage of glycosidic bond.

4. Orotic aciduria  & Reye’s syndrome are the common disorders of pyrimidine nucleotides metabolism


  1. What are pyrimidines, and why are they important in biology? Pyrimidines are a class of organic molecules consisting of a six-membered ring structure with two nitrogen atoms. They are essential components of nucleic acids (DNA and RNA) and play critical roles in transmitting genetic information, protein synthesis, and cellular metabolism. Without pyrimidines, the fundamental processes of life would be impossible.
  2. How is the biosynthesis of pyrimidine regulated within cells? The biosynthesis of pyrimidine is tightly regulated through feedback inhibition and allosteric regulation mechanisms. Key enzymes in the pathway are inhibited by the end products of the pathway to prevent overproduction of pyrimidines. Additionally, allosteric regulators modulate enzyme activity in response to cellular demands, ensuring that pyrimidine synthesis is finely tuned to meet the needs of the cell.
  3. What disorders are associated with dysregulation of pyrimidine biosynthesis? Dysregulation of pyrimidine biosynthesis can lead to various disorders, including orotic aciduria, a rare metabolic disorder characterized by the excessive excretion of orotic acid in urine. Other conditions may arise due to deficiencies in pyrimidine nucleotides, affecting processes such as DNA replication, repair, and cell proliferation.
  4. What are some applications of understanding pyrimidine biosynthesis in medicine and agriculture? Understanding pyrimidine biosynthesis is crucial for developing therapeutics targeting nucleic acid metabolism, including anticancer drugs and antiviral agents. Additionally, insights into pyrimidine biosynthesis pathways are valuable for improving crop yields and enhancing stress tolerance in agricultural plants through biotechnological interventions.
  5. What are the current areas of research focus in pyrimidine biosynthesis? Current research in pyrimidine biosynthesis focuses on elucidating the molecular mechanisms underlying pathway regulation, identifying novel drug targets for therapeutic intervention, and exploring the evolutionary conservation of pyrimidine biosynthesis across diverse organisms. Additionally, efforts are directed towards developing innovative biotechnological applications of pyrimidine metabolism in fields such as medicine, agriculture, and biotechnology.

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