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
Loading the 3D model…
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).
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
Related conditions
Related
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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: CAD: Multifunctional protein CAD (human) (UniProt, 2026); Pyrimidine biosynthesis (Reactome, 2026); 4C6E: Crystal structure of the dihydroorotase domain of human CAD bound to substrate at pH 5.5 (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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.