Target type: biologicalprocess
The chemical reactions and pathways resulting in the breakdown of dUMP, deoxyuridine (5'-)monophosphate. [GOC:go_curators]
The dUMP catabolic process is a critical metabolic pathway responsible for the degradation of dihydrouracil monophosphate (dUMP), a nucleoside monophosphate that arises from the breakdown of DNA and RNA. This process is essential for maintaining cellular homeostasis and preventing the accumulation of potentially toxic dUMP metabolites.
The pathway begins with the reduction of dUMP to dihydrouracil (DHU) by the enzyme dihydropyrimidine dehydrogenase (DPD). This step is critical as it prevents the accumulation of dUMP, which can inhibit the synthesis of thymidine monophosphate (TMP), an essential precursor for DNA synthesis.
DHU is then further metabolized by the enzyme dihydropyrimidinase (DHP), which hydrolyzes DHU to β-ureidopropionic acid (β-UPA). This reaction releases ammonia and carbon dioxide as byproducts.
Finally, β-UPA is converted to β-alanine by the enzyme β-ureidopropionase (BUP), which cleaves the urea moiety from β-UPA. β-alanine is then further metabolized by cellular processes or excreted from the cell.
The dUMP catabolic process plays a vital role in maintaining cellular health by ensuring the proper degradation of dUMP and preventing its accumulation. Defects in this pathway can lead to a variety of health issues, including cancer and neurological disorders. This is because dUMP accumulation can disrupt DNA synthesis, leading to cell cycle arrest and apoptosis, while also interfering with the normal functioning of various cellular processes.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Uridine phosphorylase 1 | A uridine phosphorylase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16831] | Homo sapiens (human) |
| Dihydropyrimidine dehydrogenase [NADP(+)] | A dihydropyrimidine dehydrogenase [NADP(+)] that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q12882] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| doxifluridine | doxifluridine : A pyrimidine 5'-deoxyribonucleoside that is 5-fluorouridine in which the hydroxy group at the 5' position is replaced by a hydrogen. It is an oral prodrug of the antineoplastic agent 5-fluorouracil. Designed to circumvent the rapid degradation of 5-fluorouracil by dihydropyrimidine dehydrogenase in the gut wall, it is converted into 5-fluorouracil in the presence of pyrimidine nucleoside phosphorylase. | organofluorine compound; pyrimidine 5'-deoxyribonucleoside | antimetabolite; antineoplastic agent; prodrug |
| eniluracil | eniluracil: structure in first source; inactivates dihydropyrimidine dehydrogenase | pyrimidone | |
| 5-benzylacyclouridine | 5-benzyl-1-(2-hydroxyethoxymethyl)uracil : A pyrimidone that is uracil which is substituted by a 2-hydroxyethoxymethyl group at position 1 and a benzyl group at position 5. 5-benzylacyclouridine: structure given in first source | hydroxyether; primary alcohol; pyrimidone | |
| 5-iodouracil | 5-iodouracil : An organoiodine compound consisting of uracil having an iodo substituent at the 5-position. 5-iodouracil: RN given refers to parent cpd | organoiodine compound | antimetabolite |
| 5-cyanouracil | |||
| 3-cyano-6-hydroxy-4-methyl-2-pyridone | 3-cyano-6-hydroxy-4-methyl-2-pyridone: structure in first source | ||
| 5-vinyluracil | 5-vinyluracil: RN given refers to unlabeled parent cpd | ||
| 2,6-dihydroxy-3-cyanopyridine | 2,6-dihydroxy-3-cyanopyridine: inhibitor of 5-fluorouracil degradation |