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

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 nucleotide

  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

  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 orotate

  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

       Pyrimidine undergoes similar

       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 &

       These compounds gets metabolise and
excreted through urine

Disorders of pyrimidine

       Orotic aciduria

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


  • Aspartate
    + Glutamine + Co2 contribute for pyrimidine ring

  • Proceeds
    only in a cytoplasm of cells

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

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

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