Biochemistry · Enzyme
Ornithine transcarbamylase (OTC) !
OTC joins carbamoyl phosphate to ornithine to make citrulline. Its X-linked deficiency is the most common urea cycle disorder.
Updated 2026-11-01
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Key facts
- Carbamoyl phosphate + ornithine → citrulline + Pi, in the mitochondrial matrix.
- Its gene is on the X chromosome: males fall ill early and carrier females may have symptoms.
- If it is missing, carbamoyl phosphate spills into the cytosol and forms orotic acid through the pyrimidine pathway.
- It is a trimer; ornithine enters the mitochondrion through the ORNT1 carrier.
Structure
- 1OTH shows human OTC with PALO, an analogue that mimics both substrates joined in the transition state.
Regulation
- It has no important allosteric control: it follows the supply of ornithine and carbamoyl phosphate.
Inhibitors and toxins
- PALO (N-phosphonacetyl-L-ornithine), an experimental inhibitor.
Clinical notes
- OTC deficiency: hyperammonaemia, high urinary orotic acid and low plasma citrulline.
- In hereditary orotic aciduria (UMP synthase) orotic acid also rises, but there is no hyperammonaemia and there is megaloblastic anaemia.
- Carriers may decompensate after childbirth, during fasting or with valproate.
Pathways
Related conditions
Related
Test yourself
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How is OTC deficiency inherited?
X-linked: hemizygous males have the severe forms and some carrier females have symptoms because of X inactivation.
Why does orotic acid rise when OTC is missing?
Spare carbamoyl phosphate leaves for the cytosol and enters the pyrimidine pathway, which makes orotate.
How is it told apart from hereditary orotic aciduria?
OTC deficiency has hyperammonaemia; hereditary orotic aciduria does not, and shows megaloblastic anaemia instead.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: OTC: Ornithine transcarbamylase, mitochondrial (human) (UniProt, 2026); OTC gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1OTH: CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH N-PHOSPHONACETYL-L-ORNITHINE (RCSB Protein Data Bank, 2026).
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