Biochemistry · Enzyme
UMP synthase !
Finishes the first pyrimidine: joins orotate to ribose phosphate and turns it into UMP. Its loss causes orotic aciduria.
Updated 2026-11-01
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Key facts
- Two activities in one protein: OPRT (orotate + PRPP → OMP + PPi) and ODC (OMP → UMP + CO₂).
- OMP decarboxylase is one of the most efficient enzymes known and uses no cofactor.
- Autosomal recessive deficiency: hereditary orotic aciduria, with megaloblastic anaemia unresponsive to B12 or folate.
- OPRT also activates 5-fluorouracil to FUMP.
- Also called
- Orotate phosphoribosyltransferase + OMP decarboxylase
- EC number
- 2.4.2.10, 4.1.1.23
- Genes
- UMPS
- Structure (PDB)
- 2QCD
Regulation
- Mainly regulated by orotate and PRPP supply; UMP inhibits ODC.
Inhibitors and toxins
- 6-Azauridine (as the monophosphate, ODC)
- Oxypurinol ribonucleotide (ODC, mild effect)
Clinical notes
- In orotic aciduria, oral uridine bypasses the block (uridine kinase → UMP) and turns down CPS-II.
- Allopurinol can mildly raise urinary orotic acid by inhibiting ODC.
- Low tumour OPRT activity is linked to a poorer response to 5-FU.
Pathways
Related conditions
Related
- Orotic acid
- PRPP (phosphoribosyl pyrophosphate)
- Dihydroorotate dehydrogenase (DHODH)
- CAD (carbamoyl phosphate synthetase II)
- Drugs acting on nucleotide metabolism
Test yourself
Think of the answer, then tap the question to see it.
Which two reactions does UMP synthase perform?
It joins orotate and PRPP (OMP, via OPRT) and then decarboxylates OMP to UMP (via ODC).
Why does the anaemia of orotic aciduria not improve with B12 or folate?
The defect lies in pyrimidine synthesis, not folate: without UMP, blood precursors lack nucleotides for DNA.
How does uridine work in orotic aciduria?
It is phosphorylated to UMP without UMP synthase and, as UTP rises, it turns down CPS-II and orotate production.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: UMPS: Uridine 5'-monophosphate synthase (human) (UniProt, 2026); 2QCD: Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to UMP (RCSB Protein Data Bank, 2026); 2WNS: Human Orotate phosphoribosyltransferase (OPRTase) domain of Uridine 5' -monophosphate synthase (UMPS) in complex with its substrate orotidine 5'-monophosphate (OMP) (RCSB Protein Data Bank, 2026); Pyrimidine biosynthesis (Reactome, 2026).
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Representative model, for educational purposes only.