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[Biochemistry](https://durgical.com/en/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](https://www.enzyme-database.org/query.php?ec=2.4.2.10, 4.1.1.23)

**Genes**
UMPS

**Structure (PDB)**
[2QCD](https://www.rcsb.org/structure/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

- [Pyrimidine synthesis](https://durgical.com/en/biochemistry/pathways/pyrimidine-synthesis/)

## Related conditions

- [Hereditary orotic aciduria](https://durgical.com/en/conditions/hereditary-orotic-aciduria/)

## Related

- [Orotic acid](https://durgical.com/en/biochemistry/molecules/orotic-acid/)
- [PRPP (phosphoribosyl pyrophosphate)](https://durgical.com/en/biochemistry/molecules/prpp/)
- [Dihydroorotate dehydrogenase (DHODH)](https://durgical.com/en/biochemistry/enzymes/dihydroorotate-dehydrogenase/)
- [CAD (carbamoyl phosphate synthetase II)](https://durgical.com/en/biochemistry/enzymes/cad/)
- [Drugs acting on nucleotide metabolism](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [UMPS: Uridine 5'-monophosphate synthase (human)](https://www.uniprot.org/uniprotkb/P11172/entry) (UniProt, 2026); [2QCD: Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to UMP](https://www.rcsb.org/structure/2QCD) (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)](https://www.rcsb.org/structure/2WNS) (RCSB Protein Data Bank, 2026); [Pyrimidine biosynthesis](https://reactome.org/PathwayBrowser/#/R-HSA-500753) (Reactome, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/ump-synthase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/ump-synthase/