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

# CAD (carbamoyl phosphate synthetase II)

A single protein performs the first three steps of pyrimidine synthesis; its CPS-II part is the pathway's control point.

Updated 2026-11-01

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## Key facts

- CAD = Carbamoyl phosphate synthetase II + Aspartate transcarbamoylase + Dihydroorotase.
- CPS-II: glutamine + HCO₃⁻ + 2 ATP → carbamoyl phosphate; it is cytosolic.
- UTP inhibits it and PRPP and ATP activate it; it is the rate-limiting step in humans.
- CPS-I, by contrast, is mitochondrial, uses ammonia and needs N-acetylglutamate (urea cycle).

**Also called**
CPS-II, Multifunctional protein CAD

**EC number**
[6.3.5.5](https://www.enzyme-database.org/query.php?ec=6.3.5.5)

**Genes**
CAD

**Structure (PDB)**
[4C6E](https://www.rcsb.org/structure/4C6E)

## Regulation

- UTP: end-product inhibition.
- PRPP and ATP: activation.
- Phosphorylation by MAP kinase (ERK) and the mTORC1–S6K pathway activates it when the cell proliferates; PKA fine-tunes it.

## Inhibitors and toxins

- PALA (aspartate transcarbamoylase)
- Acivicin (glutamine analogue)

## Clinical notes

- CAD deficiency causes an infantile epileptic encephalopathy with anaemia; oral uridine can improve it greatly.
- Because it is cytosolic and uses glutamine, CPS-II takes no part in ammonia disposal.
- The 3D structure shown is the dihydroorotase domain of human CAD with its substrate.

## 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

- [Dihydroorotate dehydrogenase (DHODH)](https://durgical.com/en/biochemistry/enzymes/dihydroorotate-dehydrogenase/)
- [UMP synthase](https://durgical.com/en/biochemistry/enzymes/ump-synthase/)
- [Orotic acid](https://durgical.com/en/biochemistry/molecules/orotic-acid/)
- [PRPP (phosphoribosyl pyrophosphate)](https://durgical.com/en/biochemistry/molecules/prpp/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which three activities does the CAD protein combine?

Carbamoyl phosphate synthetase II, aspartate transcarbamoylase and dihydroorotase: steps 1 to 3 of pyrimidine synthesis.

## Which molecule inhibits CPS-II, and which activates it?

UTP (end product) inhibits it and PRPP activates it.

## Where does CPS-II get its nitrogen?

From the amide group of glutamine, not from free ammonia as CPS-I does.

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

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

Sources: [CAD: Multifunctional protein CAD (human)](https://www.uniprot.org/uniprotkb/P27708/entry) (UniProt, 2026); [Pyrimidine biosynthesis](https://reactome.org/PathwayBrowser/#/R-HSA-500753) (Reactome, 2026); [4C6E: Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 5.5](https://www.rcsb.org/structure/4C6E) (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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