Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

Official Name

argininosuccinate synthase

Name from literature

argininosuccinic acid synthetase

Pathway from literature

urea production/urea cycle

Pathway from KEGG

Amino Acid Metabolism; Urea cycle and metabolism of amino groups; map00220

Amino Acid Metabolism; Arginine and proline metabolism; map00330

Amino Acid Metabolism; Alanine and aspartate metabolism; map00252


Human (9606)

Genome localization

9q34.1[445 ],

Rate-limiting Description

"The enzyme argininosuccinate synthetase (ASS) is the rate limiting enzyme in the metabolic pathway leading from L-citrulline to L-arginine, the physiological substrate of all isoforms of nitric oxide synthases (NOS)." (11556547)

"Evidence suggests that argininosuccinate synthase activity is rate-limiting to high-output NO synthesis and, hence, represents a novel target for the treatment of pathophysiological conditions arising from NO overproduction." (10709858)

Regulatory Information

Upstream transcription factor


Regulatory type


transcriptional factor;c-myc(4609)

"ASS, the c-myc-regulated gene is involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV.#argininosuccinate synthetase gene expression is stimulated by glutamine through cytosolic O-glycosylation of Sp1 in tumor cells.#HSCARG regulation of argininosuccinate synthetase activity is crucial for maintaining the intracellular balance between redox state and nitric oxide levels." (16703398#14570901#18263583)

key enzyme;

"ASS is a key enzyme which converts citrulline to arginine." (18473854)

transcriptional level;"TNF-alpha(7124),"

"high levels of AS expression, which may be required for several arginine-dependent processes in cancer, including the production of nitric oxide, proline, pyrimidines and polyamines, is regulated by TNF-alpha" (17354225)





Gene ontology

Gene ontology

GO:0006526 (P) arginine biosynthetic process [Q5T6L4, P00966, Q5T6L6, A8KAP9 ];
GO:0000050 (P) urea cycle [P00966 ];
GO:0004055 (F) argininosuccinate synthase activity [Q5T6L4, P00966, Q5T6L6, A8KAP9 ];
GO:0005737 (C) cytoplasm [P00966 ];
GO:0005515 (F) protein binding [P00966 ];
GO:0005524 (F) ATP binding [Q5T6L4, P00966, Q5T6L6, A8KAP9 ];

Disease relevance


Defects in ASS1 are the cause of citrullinemia type 1 (CTLN1) [MIM:215700]. Citrullinemia belongs to the urea cycle disorders. It is an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. CTLN1 usually manifests in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder CTLN1 form can develop later in childhood or adulthood [P00966 ];



A8KAP9; P00966; Q5T6L4; Q5T6L6

Entrez Gene




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  Last Modified: 2009-03-24  
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