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 undergo degradation after a certain period.

Pyrimidine Catabolism Steps

The catabolism of pyrimidine nucleotides is explained in a few steps.

Step 1: Nucleotide to nucleoside

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

Step 2: Deamination

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

Step 3: Phosphorylation

• Uridine and deoxythymidine (in the case of DNA) are 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: Dehydration

• Uracil and thymine are 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: Cyclization

• DihydroUracil and dihydroThymine are 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 a particular place.

Step 6: Deamination

• β-Urido propionate and β-urido isobutyrate are 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: Transamination

• The β-alanine and β-amino Isobutyrate is converted into Malonic semialdehyde and Methylmalonic semialdehyde by transamination process.
• This reaction is catalyzed by aminotransferase and the second substrate is α-ketoglutarate and the secondary product is Glutamine.

Step 8: hydration

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

Conclusion

The Pyrimidine catabolism pathway generally leads to NH₄⁺ production and thus to urea synthesis.

• Pyrimidine Synthesis Pathway: Synthesis of pyrimidine derivatives
• Pyrimidine Catabolism: UMP and CMP degradation Pathway
• Purine Catabolism and its Uric Acid formation
• Purine Synthesis: Synthesis of Purine RiboNucleotides

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.