Pyrimidine Catabolism: UMP and CMP degradation Pathway

Pyrimidine catabolism is the process of excreting pyrimidine molecules from the body. It is a critical part of DNA synthesis and repair.

This blog is all about pyrimidine catabolism. Specifically, it covers the following topics:

What is pyrimidine catabolism, and what are the main causes? Pyrimidine catabolism is the process of breaking down pyrimidine molecules into smaller molecules. The main causes of pyrimidine catabolism are viral attacks, cancerous tumors, and burns.
What are the different types of pyrimidine catabolism?
There are two main types of pyrimidine catabolism: denovo and salvage. When new pyrimidines are created from ammonia sources, de novo pyrimidine catabolism occurs. Salvage pyrimidine catabolism occurs when excess pyrimidines are recycled from other parts of the body, such as the liver or kidneys.
How does pyrimidine catabolism help us understand how the body works? The pyrimidine pathway helps us understand how the body works. The pyrimidine pathway helps the body create important molecules like DNA and proteins.

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.

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.

Pyrimidine Catabolism: UMP and CMP degradation Pathway