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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-06-13 18:31:55 UTC
HMDB IDHMDB00052
Secondary Accession Numbers
  • HMDB01006
Metabolite Identification
Common NameArgininosuccinic acid
DescriptionArginosuccinic acid is a basic amino acid. Some cells synthesize it from citrulline, aspartic acid and use it as a precursor for arginine in the urea cycle or Citrulline-NO cycle. The enzyme that catalyzes the reaction is argininosuccinate synthetase. Argininosuccinic acid is a precursor to fumarate in the citric acid cycle via argininosuccinate lyase. Defects in the arginosuccinate lyase enzyme can lead to arginosuccinate lyase deficiency. Argininosuccinate (ASA) lyase deficiency results in defective cleavage of ASA. This leads to an accumulation of ASA in cells and an excessive excretion of ASA in urine (arginosuccinic aciduria). In virtually all respects, this disorder shares the characteristics of other urea cycle defects. The most important characteristic of ASA lyase deficiency is its propensity to cause hyperammonemia in affected individuals. ASA in affected individuals is excreted by the kidney at a rate practically equivalent to the glomerular filtration rate (GFR). Whether ASA itself causes a degree of toxicity due to hepatocellular accumulation is unknown; such an effect could help explain hyperammonemia development in affected individuals. Regardless, the name of the disease is derived from the rapid clearance of ASA in urine, although elevated levels of ASA can be found in plasma. ASA lyase deficiency is associated with high mortality and morbidity rates. Symptoms of ASA lyase deficiency include anorexia, irritability rapid breathing, lethargy and vomiting. Extreme symptoms include coma and cerebral edema.
Structure
Thumb
Synonyms
  1. 2-(N(Omega)-L-arginine)succinate
  2. 2-(N(Omega)-L-arginine)succinic acid
  3. 2-(N(Omega)-L-arginino)succinate
  4. 2-(N(Omega)-L-arginino)succinic acid
  5. 2-(Nw-L-arginino)butanedioate
  6. 2-(Nw-L-arginino)butanedioic acid
  7. Argininosuccinate
  8. Argininosuccinic acid
  9. Arginosuccinate
  10. Arginosuccinic acid
  11. ASA
  12. L-Argininosuccinate
  13. L-Argininosuccinic acid
  14. L-Arginosuccinate
  15. L-Arginosuccinic acid
  16. N(Omega)-(L-arginino)succinate
  17. N(Omega)-(L-arginino)succinic acid
  18. N-(((4-Amino-4-carboxybutyl)amino)iminomethyl)-L-Aspartate
  19. N-(((4-Amino-4-carboxybutyl)amino)iminomethyl)-L-Aspartic acid
  20. N-(L-Arginino) succinate
  21. N-(L-Arginino) succinic acid
  22. N-(L-Arginino)succinate
  23. N-(L-Arginino)succinic acid
  24. N-[(4-Amino-4-carboxybutyl)amidino]-L-Aspartate
  25. N-[(4-Amino-4-carboxybutyl)amidino]-L-Aspartic acid
  26. N-[[(4-Amino-4-carboxybutyl)amino]iminomethyl]-L-Aspartate
  27. N-[[(4-Amino-4-carboxybutyl)amino]iminomethyl]-L-Aspartic acid
Chemical FormulaC10H18N4O6
Average Molecular Weight290.2731
Monoisotopic Molecular Weight290.122634328
IUPAC Name(2S)-2-{1-[(4S)-4-amino-4-carboxybutyl]carbamimidamido}butanedioic acid
Traditional IUPAC Name(2S)-2-{1-[(4S)-4-amino-4-carboxybutyl]carbamimidamido}butanedioic acid
CAS Registry Number2387-71-5
SMILES
N[C@@H](CCCNC(=N)N[C@@H](CC(O)=O)C(O)=O)C(O)=O
InChI Identifier
InChI=1S/C10H18N4O6/c11-5(8(17)18)2-1-3-13-10(12)14-6(9(19)20)4-7(15)16/h5-6H,1-4,11H2,(H,15,16)(H,17,18)(H,19,20)(H3,12,13,14)/t5-,6-/m0/s1
InChI KeyKDZOASGQNOPSCU-WDSKDSINSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aliphatic Acyclic Compounds
  • Other amino acids(KEGG)
Substituents
  • Carboxylic Acid
  • Guanidine
  • Primary Aliphatic Amine (Alkylamine)
  • Succinic Acid
  • Tricarboxylic Acid Derivative
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.46 g/LALOGPS
logP-3.2ALOGPS
logP-5.8ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)2.14ChemAxon
pKa (Strongest Basic)12.39ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area185.83ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity75.31ChemAxon
Polarizability27.6ChemAxon
Spectra
SpectraGC-MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020map00330
Aspartate MetabolismSMP00067map00250
Urea CycleSMP00059map00330
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected and Quantified0.0032(0.00-0.0065) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified300.0 (270.0-458.0) uMChildren (1-13 years old)FemaleArgininosuccinyl-CoA lyase deficiency details
UrineDetected and Quantified0.65 (0.0-1.3) umol/mmol creatinineChildren (1-13 years old)BothArgininemia details
UrineDetected and Quantified1542.00 umol/mmol creatinineAdult (>18 years old)BothArgininosuccinic aciduria (ASL) details
Associated Disorders and Diseases
Disease References
Argininemia
  1. MetaGene
Argininosuccinic aciduria
  1. Renner C, Sewell AC, Bervoets K, Forster H, Bohles H: Sodium citrate supplementation in inborn argininosuccinate lyase deficiency: a study in a 5-year-old patient under total parenteral nutrition. Eur J Pediatr. 1995 Nov;154(11):909-14. Pubmed: 8582405
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021885
KNApSAcK IDNot Available
Chemspider ID16059
KEGG Compound IDC03406
BioCyc IDNot Available
BiGG ID41790
Wikipedia LinkArgininosuccinic acid
NuGOwiki LinkHMDB00052
Metagene LinkHMDB00052
METLIN ID5115
PubChem Compound16950
PDB IDNot Available
ChEBI ID15682
References
Synthesis ReferenceHagino, Koji; Nakanishi, Toshihide. Fermentative production of L-arginosuccinic acid. Jpn. Kokai Tokkyo Koho (1980), 3 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Kleijer WJ, Garritsen VH, Linnebank M, Mooyer P, Huijmans JG, Mustonen A, Simola KO, Arslan-Kirchner M, Battini R, Briones P, Cardo E, Mandel H, Tschiedel E, Wanders RJ, Koch HG: Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families. J Inherit Metab Dis. 2002 Sep;25(5):399-410. Pubmed: 12408190
  2. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  3. Michels VV, Beaudet AL: Arginase deficiency in multiple tissues in argininemia. Clin Genet. 1978 Jan;13(1):61-7. Pubmed: 624188
  4. Glick NR, Snodgrass PJ, Schafer IA: Neonatal argininosuccinic aciduria with normal brain and kidney but absent liver argininosuccinate lyase activity. Am J Hum Genet. 1976 Jan;28(01):22-30. Pubmed: 174426
  5. Pelli N, Fensom AH, Slade C, Boa F, Mieli-Vergani G, Vergani D: Argininosuccinate lyase: a new autoantigen in liver disease. Clin Exp Immunol. 1998 Dec;114(3):455-61. Pubmed: 9844057
  6. Scaglia F, Brunetti-Pierri N, Kleppe S, Marini J, Carter S, Garlick P, Jahoor F, O'Brien W, Lee B: Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism. J Nutr. 2004 Oct;134(10 Suppl):2775S-2782S; discussion 2796S-2797S. Pubmed: 15465784
  7. Cohen BD: Methyl group deficiency and guanidino production in uremia. Mol Cell Biochem. 2003 Feb;244(1-2):31-6. Pubmed: 12701806
  8. Au WL, Lim TC, Seow DC, Koh PL, Loh NK, Lim MS, Tan IK, Yee WC: Serial diffusion-weighted magnetic resonance imaging in adult-onset citrullinaemia. J Neurol Sci. 2003 May 15;209(1-2):101-4. Pubmed: 12686410
  9. Wasant P, Srisomsap C, Liammongkolkul S, Svasti J: Urea cycle disorders in Thai infants: a report of 5 cases. J Med Assoc Thai. 2002 Aug;85 Suppl 2:S720-31. Pubmed: 12403252
  10. Reid Sutton V, Pan Y, Davis EC, Craigen WJ: A mouse model of argininosuccinic aciduria: biochemical characterization. Mol Genet Metab. 2003 Jan;78(1):11-6. Pubmed: 12559843
  11. Fleisher LD, Rassin DK, Desnick RJ, Salwen HR, Rogers P, Bean M, Gaull GE: Argininosuccinic aciduria: prenatal studies in a family at risk. Am J Hum Genet. 1979 Jul;31(4):439-45. Pubmed: 484552

Enzymes

General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
ADSL
Uniprot ID:
P30566
Molecular weight:
54888.735
General function:
Involved in argininosuccinate synthase activity
Specific function:
Not Available
Gene Name:
ASS1
Uniprot ID:
P00966
Molecular weight:
46530.055
Reactions
Adenosine triphosphate + Citrulline + L-Aspartic acid → Adenosine monophosphate + Pyrophosphate + Argininosuccinic aciddetails
Adenosine triphosphate + Citrulline + L-Aspartic acid → Adenosine monophosphate + Pyrophosphate + Argininosuccinic aciddetails
General function:
Involved in argininosuccinate lyase activity
Specific function:
Not Available
Gene Name:
ASL
Uniprot ID:
P04424
Molecular weight:
51657.505
Reactions
Argininosuccinic acid → Fumaric acid + L-Argininedetails
General function:
Involved in phosphotransferase activity, for other substituted phosphate groups
Specific function:
Catalyzes phosphatidylcholine biosynthesis from CDP-choline. It thereby plays a central role in the formation and maintenance of vesicular membranes.
Gene Name:
CHPT1
Uniprot ID:
Q8WUD6
Molecular weight:
45096.535
References
  1. O KM, Choy PC: Effects of fasting on phosphatidylcholine biosynthesis in hamster liver: regulation of cholinephosphotransferase activity by endogenous argininosuccinate. Biochem J. 1993 Feb 1;289 ( Pt 3):727-33. Pubmed: 8382048
General function:
Involved in argininosuccinate synthase activity
Specific function:
ATP + L-citrulline + L-aspartate = AMP + diphosphate + N(omega)-(L-arginino)succinate
Gene Name:
ASS1
Uniprot ID:
Q5T6L4
Molecular weight:
46530.1