Human Metabolome Database Version 3.5

Showing metabocard for Argininosuccinic acid (HMDB00052)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:07:49 -0700
HMDB ID HMDB00052
Secondary Accession Numbers
  • HMDB01006
Metabolite Identification
Common Name Argininosuccinic acid
Description Arginosuccinic 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
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C10H18N4O6
Average Molecular Weight 290.2731
Monoisotopic Molecular Weight 290.122634328
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 Number 2387-71-5
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 Key KDZOASGQNOPSCU-WDSKDSINSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Amino Acids, Peptides, and Analogues
Class Amino Acids and Derivatives
Sub Class Alpha 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 Parent Alpha Amino Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
Application Not Available
Cellular locations
  • Cytoplasm
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.46 g/L ALOGPS
LogP -3.25 ALOGPS
LogP -5.8 ChemAxon
LogS -2.80 ALOGPS
pKa (strongest acidic) 2.14 ChemAxon
pKa (strongest basic) 12.39 ChemAxon
Hydrogen Acceptor Count 10 ChemAxon
Hydrogen Donor Count 7 ChemAxon
Polar Surface Area 185.83 A2 ChemAxon
Rotatable Bond Count 9 ChemAxon
Refractivity 75.31 ChemAxon
Polarizability 27.6 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Prostate
Pathways
Name SMPDB Link KEGG Link
Arginine and Proline Metabolism SMP00020 map00330 Link_out
Aspartate Metabolism SMP00067 map00250 Link_out
Urea Cycle SMP00059 map00330 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Urine Detected and Quantified
0.0032(0.00-0.0065) umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 300.0 (270.0-458.0) uM Children (1-13 year old) Female Sodium citrate supplementation in Argininosuccinyl-CoA lyase deficiency
Urine Detected and Quantified 0.65 (0.0-1.3) umol/mmol creatinine Children (1-13 year old) Both Argininemia
Urine Detected and Quantified 1542.00 umol/mmol creatinine Adult (>18 years old) Both Argininosuccinicaciduria
Associated Disorders and Diseases
Disease References
Argininosuccinic aciduria
  • 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 Link_out
      Argininemia
          Associated OMIM IDs
          DrugBank ID Not Available
          DrugBank Metabolite ID Not Available
          Phenol Explorer Compound ID Not Available
          Phenol Explorer Metabolite ID Not Available
          FoodDB ID FDB021885
          KNApSAcK ID Not Available
          Chemspider ID 16059 Link_out
          KEGG Compound ID C03406 Link_out
          BioCyc ID Not Available
          BiGG ID 41790 Link_out
          Wikipedia Link Argininosuccinic acid Link_out
          NuGOwiki Link HMDB00052 Link_out
          Metagene Link HMDB00052 Link_out
          METLIN ID 5115 Link_out
          PubChem Compound 16950 Link_out
          PDB ID Not Available
          ChEBI ID 15682 Link_out
          References
          Synthesis Reference Hagino, 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. Michels VV, Beaudet AL: Arginase deficiency in multiple tissues in argininemia. Clin Genet. 1978 Jan;13(1):61-7. Pubmed: 624188 Link_out
          2. 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 Link_out
          3. 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 Link_out
          4. 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 Link_out
          5. Cohen BD: Methyl group deficiency and guanidino production in uremia. Mol Cell Biochem. 2003 Feb;244(1-2):31-6. Pubmed: 12701806 Link_out
          6. 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 Link_out
          7. 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 Link_out
          8. 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 Link_out
          9. 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 Link_out
          10. 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 Link_out
          11. 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 Link_out

          Enzymes
          Name: Adenylosuccinate lyase
          Reactions: Not Available
          Gene Name: ADSL
          Uniprot ID: P30566 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Argininosuccinate synthase
          Reactions:
          Adenosine triphosphate + Citrulline + L-Aspartic acid unknown Adenosine monophosphate + Pyrophosphate + Argininosuccinic acid details
          Adenosine triphosphate + Citrulline + L-Aspartic acid unknown Adenosine monophosphate + Pyrophosphate + Argininosuccinic acid details
          Gene Name: ASS1
          Uniprot ID: P00966 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Argininosuccinate lyase
          Reactions:
          Argininosuccinic acid unknown Fumaric acid + L-Arginine details
          Gene Name: ASL
          Uniprot ID: P04424 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Cholinephosphotransferase 1
          Reactions: Not Available
          Gene Name: CHPT1
          Uniprot ID: Q8WUD6 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Argininosuccinate synthase
          Reactions: Not Available
          Gene Name: ASS1
          Uniprot ID: Q5T6L4 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA