[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Ornithine transcarbamylase (OTC)

[Biochemistry](https://durgical.com/en/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.

**EC number**
[2.1.3.3](https://www.enzyme-database.org/query.php?ec=2.1.3.3)

**Genes**
OTC

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

## 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

- [Urea cycle](https://durgical.com/en/biochemistry/pathways/urea-cycle/)

## Related conditions

- [Ornithine transcarbamylase (OTC) deficiency](https://durgical.com/en/conditions/ornithine-transcarbamylase-deficiency/)
- [Hyperammonaemia](https://durgical.com/en/conditions/hyperammonaemia/)

## Related

- [Carbamoyl phosphate synthetase I (CPS-I)](https://durgical.com/en/biochemistry/enzymes/carbamoyl-phosphate-synthetase-i/)
- [Argininosuccinate synthetase (ASS)](https://durgical.com/en/biochemistry/enzymes/argininosuccinate-synthetase/)

## 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.

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

Sources: [OTC: Ornithine transcarbamylase, mitochondrial (human)](https://www.uniprot.org/uniprotkb/P00480/entry) (UniProt, 2026); [OTC gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/otc/) (MedlinePlus, US National Library of Medicine, 2026); [1OTH: CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH N-PHOSPHONACETYL-L-ORNITHINE](https://www.rcsb.org/structure/1OTH) (RCSB Protein Data Bank, 2026).

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