Pyrimidine Catabolism : UMP and CMP degradation Pathway

Animal cells degrade pyrimidine nucleotides (Pyrimidine Catabolism Pathway) to their component bases. These reactions, like those of purine nucleotides, occur through Dephosphorylation, Deamination and Glycosidic bond cleavages. After Pyrimidine biosynthesis, the newly synthesized molecules undergoes degradation after certain period.

Pyrimidine Catabolism Steps:

The catabolism of pyrimidine nucleotides are explained in few steps.

Pyrimidine Catabolism Pathway Steps

Step 1:

  • CMP, UMP and deoxyIMP is converted into Cytidine, Uridine deoxythymidine.
  • This reaction is catalyzed by the enzyme Nucleotidase.

Step 2:

  • Cytidine is deaminated into Uridine. This reaction is catalyzed by “Cytidine deaminase”.

Step 3:

  • Uridine and deoxy thymidine (in case of DNA) is converted into Uracine and Thymidine.
  • This reaction is catalyzed by Uridine phosphorylase.
  • Here on inorganic phosphate is substituted on the first carbon of hydrolyzed Glycosidic linkage sugar molecule.
  • The sugar molecule is released as in the form of Ribose-1-Phosphate and deoxy Ribose-1-Phosphate.

Step 4:

  • Uracil and thymine is converted into dihydroUracil and dihydroThymine.
  • This reaction is catalyzed into DihydroUracil and dihydroThymine.
  • This reaction is catalyzed by dihydro uracil dehydrogenase.
  • In this reaction one NADPH + H+ is oxidized into NADP+.

Step 5:

  • DihydroUracil and dihydroThymine is converted into β-Urido Propionate and β-urido isobutyrate.
  • This reaction is catalyzed by hydropyrimidine hydratase.
  • In this reaction the cyclized molecule is converted into linear by cleaving the covalent bond at particular place.

Step 6:

  • β-Urido propionate and β-urido isobutyrate is converted into β-alanine and β-amino isobutyrate.
  • This reaction is catalyzed by β-Urido Propionase.
  • The secondary products of this reaction are Ammonium ion (NH4+) and Carbon dioxide.

Step 7:

  • The β-alanine and β-amino Isobutyrate is converted into Malonic semialdehyde and Methyl malonic semialdehyde by transamination process.
  • This reaction is catalyzed by amino transferase and secondary substrate is α-ketoglutarate and secondary product is Glutamine.

Step 8:

  • Malonic semialdehyde and methyl malonic semialdehyde is converted into Malonyl~coA.
  • These two products are entering in the part of Fatty acid catabolism like methyl malonyl Patheway.

Conclusion:

The Pyrimidine catabolism pathway generally lead to NH4+ production and thus to urea synthesis. Thymine for example, is degraded to Methylmalonyl semialdehyde, an intermediate of Valine catabolism. It is further degraded through Propionyl~coA and Methylmalonyl~coA to Succinyl~coA.

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