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.
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
Related conditions
Related
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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: ASS1: Argininosuccinate synthase (human) (UniProt, 2026); Citrullinemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 2NZ2: Crystal structure of human argininosuccinate synthase in complex with aspartate and citrulline (RCSB Protein Data Bank, 2026).
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