thymidine catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of thymidine, deoxyribosylthymine thymine 2-deoxyriboside, a deoxynucleoside very widely distributed but occurring almost entirely as phosphoric esters in deoxynucleotides and deoxyribonucleic acid, DNA. [GOC:go_curators]

Thymidine catabolism is a metabolic pathway involved in the breakdown of thymidine, a nucleoside composed of the pyrimidine base thymine and the sugar deoxyribose. This process is essential for the recycling of nucleotide building blocks and maintaining cellular homeostasis.

Here is a detailed breakdown of the process:

1. **Thymidine phosphorylation:** Thymidine is first phosphorylated by thymidine kinase (TK) to form thymidine monophosphate (TMP). This step is crucial for trapping thymidine within the cell and preventing its leakage.
2. **Conversion to thymine:** TMP is then converted to thymine by the enzyme thymidylate phosphorylase (TP). This reaction involves the release of deoxyribose-1-phosphate (dRib-1-P).
3. **Thymine degradation:** Thymine can be further degraded by the enzyme dihydropyrimidine dehydrogenase (DPD) to dihydrothymine. Dihydrothymine is then processed by several enzymes, including beta-ureidopropionase and urease, eventually leading to the formation of carbon dioxide, water, and ammonia.

In addition to the primary catabolic pathway, there are alternative pathways for thymidine metabolism. These include:

- **Deoxyribose catabolism:** Deoxyribose-1-phosphate, generated during thymine formation, can be further degraded through a series of reactions involving deoxyribose-5-phosphate aldolase and other enzymes.
- **Thymine salvage pathway:** Thymine can be salvaged and re-incorporated into DNA by the enzyme thymidine phosphorylase.

Thymidine catabolism is tightly regulated by several factors, including the cellular concentration of thymidine, the activity of the involved enzymes, and the overall metabolic state of the cell. Defects in thymidine catabolism can lead to several diseases, including thymine-thymidine phosphorylase deficiency and DPD deficiency.

Thymidine catabolism plays a critical role in maintaining cellular homeostasis by ensuring the proper recycling of nucleotide building blocks and preventing the accumulation of potentially toxic metabolites. It is also an important target for therapeutic interventions in various diseases, including cancer and autoimmune disorders.'
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Proteins (1)

Compounds (4)