[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Argininosuccinate synthetase (ASS)

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

# Argininosuccinate synthetase (ASS)

Argininosuccinate synthetase joins citrulline and aspartate in the cytosol; this is how the second nitrogen of urea enters.

Updated 2026-11-01

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## Key facts

- Citrulline + aspartate + ATP → argininosuccinate + AMP + PPi.
- It spends two high-energy bonds, because ATP goes to AMP.
- The aspartate comes from oxaloacetate via aspartate aminotransferase.
- It is also found in kidney and endothelium, where it recycles citrulline into arginine for nitric oxide.

**EC number**
[6.3.4.5](https://www.enzyme-database.org/query.php?ec=6.3.4.5)

**Genes**
ASS1

**Structure (PDB)**
[2NZ2](https://www.rcsb.org/structure/2NZ2)

## Structure

- 2NZ2 shows the human enzyme with citrulline and aspartate in the active site.

## Regulation

- Protein-rich diets and glucocorticoids induce it; it depends on aspartate supply.

## Inhibitors and toxins

- No inhibitors are used clinically.

## Clinical notes

- Citrullinaemia type I (ASS1 gene): hyperammonaemia with very high plasma citrulline.
- Citrullinaemia type II (SLC25A13 gene, citrin): aspartate supply to the cytosol fails; it is more common in East Asia.

## Pathways

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

## Related conditions

- [Hyperammonaemia](https://durgical.com/en/conditions/hyperammonaemia/)

## Related

- [Ornithine transcarbamylase (OTC)](https://durgical.com/en/biochemistry/enzymes/ornithine-transcarbamylase/)
- [Argininosuccinate lyase (ASL)](https://durgical.com/en/biochemistry/enzymes/argininosuccinate-lyase/)
- [Aspartate aminotransferase (AST, GOT)](https://durgical.com/en/biochemistry/enzymes/aspartate-aminotransferase/)

## Test yourself

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

## Which amino acid brings the second nitrogen of urea, and at which step?

Aspartate, in the argininosuccinate synthetase reaction, in the cytosol.

## Which lab finding marks citrullinaemia type I?

Very high plasma citrulline together with hyperammonaemia.

## Why are two ATP counted at this step?

ATP splits into AMP and pyrophosphate; hydrolysis of the pyrophosphate spends another high-energy bond.

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

Sources: [ASS1: Argininosuccinate synthase (human)](https://www.uniprot.org/uniprotkb/P00966/entry) (UniProt, 2026); [Citrullinemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/citrullinemia/) (MedlinePlus, US National Library of Medicine, 2026); [2NZ2: Crystal structure of human argininosuccinate synthase in complex with aspartate and citrulline](https://www.rcsb.org/structure/2NZ2) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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