[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Dihydroorotate dehydrogenase (DHODH)

[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Dihydroorotate dehydrogenase (DHODH)

The only mitochondrial enzyme of pyrimidine synthesis; leflunomide, used in rheumatoid arthritis, blocks it.

Updated 2026-11-01

Loading the 3D model…

## Key facts

- Dihydroorotate + ubiquinone → orotate + ubiquinol.
- It sits on the outer face of the inner mitochondrial membrane and uses FMN.
- It passes electrons to coenzyme Q, linking pyrimidine synthesis with the respiratory chain.
- Teriflunomide (leflunomide's active metabolite) occupies the ubiquinone tunnel.

**EC number**
[1.3.5.2](https://www.enzyme-database.org/query.php?ec=1.3.5.2)

**Genes**
DHODH

**Structure (PDB)**
[1D3H](https://www.rcsb.org/structure/1D3H)

## Regulation

- Depends on dihydroorotate and oxidised ubiquinone supply; it slows when the respiratory chain fails.

## Inhibitors and toxins

- Leflunomide / teriflunomide
- Brequinar

## Clinical notes

- Leflunomide restrains activated T cells, which need many pyrimidines: it is used in rheumatoid arthritis.
- Teriflunomide is used in multiple sclerosis; both are teratogenic.
- DHODH variants cause Miller syndrome, with facial and limb malformations.

## Drugs that act here

- [Leflunomide](https://durgical.com/en/pharmacology/leflunomide/)

## Pathways

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

## Related conditions

- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- [Multiple sclerosis](https://durgical.com/en/conditions/multiple-sclerosis/)

## Related

- [CAD (carbamoyl phosphate synthetase II)](https://durgical.com/en/biochemistry/enzymes/cad/)
- [Orotic acid](https://durgical.com/en/biochemistry/molecules/orotic-acid/)
- [UMP synthase](https://durgical.com/en/biochemistry/enzymes/ump-synthase/)
- [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.

## Where is dihydroorotate dehydrogenase, and where do its electrons go?

In the inner mitochondrial membrane; its electrons go to ubiquinone (coenzyme Q) of the respiratory chain.

## How does leflunomide work in rheumatoid arthritis?

Its metabolite inhibits DHODH and starves activated T cells of pyrimidines, so they stop proliferating.

## Which product does DHODH form?

Orotate (orotic acid), which then receives ribose phosphate from PRPP.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/biochemistry/enzymes/dihydroorotate-dehydrogenase/)

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

Sources: [DHODH: Dihydroorotate dehydrogenase (quinone), mitochondrial (human)](https://www.uniprot.org/uniprotkb/Q02127/entry) (UniProt, 2026); [1D3H: HUMAN DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH ANTIPROLIFERATIVE AGENT A771726](https://www.rcsb.org/structure/1D3H) (RCSB Protein Data Bank, 2026); [Leflunomide: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a600032.html) (MedlinePlus, US National Library of Medicine, 2026); [Pyrimidine biosynthesis](https://reactome.org/PathwayBrowser/#/R-HSA-500753) (Reactome, 2026).

[← All of biochemistry](https://durgical.com/en/biochemistry/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

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