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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-05-20 08:11:19 UTC
HMDB IDHMDB0000797
Secondary Accession Numbers
  • HMDB0006274
  • HMDB00797
  • HMDB06274
Metabolite Identification
Common NameSAICAR
DescriptionSAICAR (or (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate) is a substrate for the multifunctional protein ADE2. SAICAR is an intermediate in purine metabolism. SAICAR is converted from 5-amino-1-(5-phospho-D-ribosyl) imidazole-4-carboxylate via phosphoribosylaminoimidazole-succinocarboxamide synthase (EC: 6.3.2.6) or SAICAR synthase. This enzyme catalyses the seventh step out of ten in the biosynthesis of purine nucleotides. The appearance of succinylaminoimidazolecarboxamide riboside (SAICAriboside) and succinyladenosine (S-Ado) in cerebrospinal fluid, in urine, and, to a lesser extent, in plasma is characteristic of a heritable deficiency known as adenylosuccinate lyase deficiency. Adenylosuccinate lyase deficiency is responsible for a range of symptoms that involve psychomotor retardation, often accompanied by epileptic seizures, and autistic features. When present in sufficiently high levels, SAICAR can act as an oncometabolite, a metabotoxin, and an acidogen. An oncometabolite is a compound that promotes tumour growth and survival. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. As an oncometabolite, high levels of SAICAR stimulate pyruvate kinase isoform M2 and promote cancer cell survival in glucose-limited conditions such as aerobic glycolysis (PMID: 23086999 ). As an organic acid, SAICAR is associated with acidosis. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of untreated adenylosuccinate lyase deficiency. Many affected children with organic acidemias experience intellectual disability or delayed development.
Structure
Thumb
Synonyms
ValueSource
(2S)-2-[5-amino-1-(5-phospho-beta-D-Ribosyl)imidazole-4-carboxamido]succinic acidChEBI
(S)-2-[5-amino-1-(5-phospho-D-Ribosyl)imidazole-4-carboxamido]succinateChEBI
1-(5'-Phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazoleChEBI
1-(5'-Phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazoleChEBI
5'-Phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazoleChEBI
SAICA ribosideChEBI
succino-AICARChEBI
Succinyl-5-aminoimidazole-4-carboxamide-1-ribose-5-phosphateChEBI
Succinylaminoimidazolecarboxamide ribose-5'-phosphateChEBI
(2S)-2-[5-amino-1-(5-phospho-b-D-Ribosyl)imidazole-4-carboxamido]succinateGenerator
(2S)-2-[5-amino-1-(5-phospho-b-D-Ribosyl)imidazole-4-carboxamido]succinic acidGenerator
(2S)-2-[5-amino-1-(5-phospho-beta-D-Ribosyl)imidazole-4-carboxamido]succinateGenerator
(2S)-2-[5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamido]succinateGenerator
(2S)-2-[5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamido]succinic acidGenerator
(S)-2-[5-amino-1-(5-phospho-D-Ribosyl)imidazole-4-carboxamido]succinic acidGenerator
Succinyl-5-aminoimidazole-4-carboxamide-1-ribose-5-phosphoric acidGenerator
Succinylaminoimidazolecarboxamide ribose-5'-phosphoric acidGenerator
(S)-2-(5-amino-1-(5-phospho-D-Ribosyl)imidazole-4-carboxamido)succinateHMDB
(S)-2-(5-amino-1-(5-phospho-D-Ribosyl)imidazole-4-carboxamido)succinic acidHMDB
(S)-2-(5-amino-1-(5-phospho-delta-Ribosyl)imidazole-4-carboxamido)succinateHMDB
(S)-2-(5-amino-1-(5-phospho-delta-Ribosyl)imidazole-4-carboxamido)succinic acidHMDB
(S)-2-[5-amino-1-(5-phospho-delta-Ribosyl)imidazole-4-carboxamido]succinateHMDB
1-(5'-Phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazole' 1-(5'-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazoleHMDB
5'-Phosphoribosyl-4-(N-succinocarbozamide)-5-aminoimidazoleHMDB
5-amino-4-Imidazole-N-succinocarboxamide ribonucleotideHMDB
L-N-[(5-amino-1-b-D-Ribofuranosylimidazol-4-yl)carbonyl]-5'-(dihydrogen phosphate)HMDB
L-N-[(5-amino-1-beta-delta-Ribofuranosylimidazol-4-yl)carbonyl]-5'-(dihydrogen phosphate)HMDB
N-(5-amino-1-Ribofuranosylimidazol-4-ylcarbonyl)aspartic acid 5'-phosphateHMDB
N-[5-amino-1-(5'-Phosphoribofuranosyl)-4-imidazolecarbonyl]aspartateHMDB
N-[5-amino-1-(5'-Phosphoribofuranosyl)-4-imidazolecarbonyl]aspartic acidHMDB
PhosphoribosylaminoimidazolesuccinocarboxamideHMDB
SAICAribosideHMDB
Succinylaminoimidazole carboxamide ribosideHMDB
Succinyl-aicarMeSH
N-(5-amino-1-beta-D-Ribofuranosylimidazole-4-carbonyl)-L-aspartic acid 5'-phosphateMeSH
5'-Phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazoleMeSH
SAICAR, (D)-isomerMeSH
Chemical FormulaC13H19N4O12P
Average Molecular Weight454.2833
Monoisotopic Molecular Weight454.073708604
IUPAC Name(2S)-2-({5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(phosphonooxy)methyl]oxolan-2-yl]-1H-imidazol-4-yl}formamido)butanedioic acid
Traditional Namesaicar
CAS Registry Number3031-95-6
SMILES
NC1=C(N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O)C(=O)N[C@@H](CC(O)=O)C(O)=O
InChI Identifier
InChI=1S/C13H19N4O12P/c14-10-7(11(22)16-4(13(23)24)1-6(18)19)15-3-17(10)12-9(21)8(20)5(29-12)2-28-30(25,26)27/h3-5,8-9,12,20-21H,1-2,14H2,(H,16,22)(H,18,19)(H,23,24)(H2,25,26,27)/t4-,5+,8+,9+,12+/m0/s1
InChI KeyNAQGHJTUZRHGAC-ZZZDFHIKSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 1-ribosyl-imidazolecarboxamides. These are organic compounds containing the imidazole ring linked to a ribose ring through a 1-2 bond.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassImidazole ribonucleosides and ribonucleotides
Sub Class1-ribosyl-imidazolecarboxamides
Direct Parent1-ribosyl-imidazolecarboxamides
Alternative Parents
Substituents
  • 1-ribosyl-imidazolecarboxamide
  • Pentose-5-phosphate
  • Pentose phosphate
  • Aspartic acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Glycosyl compound
  • N-glycosyl compound
  • Monosaccharide phosphate
  • Alpha-amino acid or derivatives
  • Pentose monosaccharide
  • 2-heteroaryl carboxamide
  • Imidazolyl carboxylic acid derivative
  • Imidazole-4-carbonyl group
  • Monoalkyl phosphate
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Alkyl phosphate
  • Dicarboxylic acid or derivatives
  • Phosphoric acid ester
  • Aminoimidazole
  • Monosaccharide
  • Imidazole
  • Heteroaromatic compound
  • Azole
  • Vinylogous amide
  • Tetrahydrofuran
  • Amino acid or derivatives
  • Carboxamide group
  • Amino acid
  • 1,2-diol
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid
  • Alcohol
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Amine
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Indirect biological role:

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 Solubility1.73 g/LALOGPS
logP-1.8ALOGPS
logP-4.8ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)1.22ChemAxon
pKa (Strongest Basic)4.54ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area263.99 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity90.65 m³·mol⁻¹ChemAxon
Polarizability38.5 ųChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05n1-9732500000-f3a7f13b1dee5f81c7a8View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-05ot-9600116000-74a62efcb34072bbe352View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-055o-1592600000-05db249dfb0f14143f9fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-3950000000-6ebf6a64483dd1392782View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001l-5940000000-e218e278f5195eb90341View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0ug3-6381900000-4fec69ff813fe652ea7dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004j-9350000000-e4e387627fbca1ef1201View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9100000000-95f6153e96335a5d2b32View in MoNA
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Locations
  • Fibroblasts
  • Intestine
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified0 uMAdult (>18 years old)Not SpecifiedNormal details
UrineDetected and Quantified<1 umol/mmol creatinineInfant (0-1 year old)MaleNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified921.0 (0.0-1842.0) uMAdult (>18 years old)Not SpecifiedAdenylosuccinate lyase (ASDL) deficiency details
Cerebrospinal Fluid (CSF)Detected but not Quantified Children (1-13 years old)FemaleATIC deficiency details
UrineDetected and Quantified<0.300 umol/mmol creatinineInfant (0-1 year old)MaleFumarase deficiency details
UrineDetected and Quantified214 umol/mmol creatinineAdult (>18 years old)BothAdenylosuccinate lyase (ASDL) deficiency details
UrineDetected but not Quantified Children (1-13 years old)FemaleATIC deficiency details
Associated Disorders and Diseases
Disease References
Fumarase deficiency
  1. Tregoning S, Salter W, Thorburn DR, Durkie M, Panayi M, Wu JY, Easterbrook A, Coman DJ: Fumarase deficiency in dichorionic diamniotic twins. Twin Res Hum Genet. 2013 Dec;16(6):1117-20. doi: 10.1017/thg.2013.72. Epub 2013 Nov 4. [PubMed:24182348 ]
ATIC deficiency
  1. Marinaki AM, Champion M, Kurian MA, Simmonds HA, Marie S, Vincent MF, van den Berghe G, Duley JA, Fairbanks LD: Adenylosuccinate lyase deficiency--first British case. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1231-3. [PubMed:15571235 ]
  2. Wevers RA, Engelke UF, Moolenaar SH, Brautigam C, de Jong JG, Duran R, de Abreu RA, van Gennip AH: 1H-NMR spectroscopy of body fluids: inborn errors of purine and pyrimidine metabolism. Clin Chem. 1999 Apr;45(4):539-48. [PubMed:10102915 ]
  3. Marie S, Heron B, Bitoun P, Timmerman T, Van Den Berghe G, Vincent MF: AICA-ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC. Am J Hum Genet. 2004 Jun;74(6):1276-81. Epub 2004 Apr 26. [PubMed:15114530 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022251
KNApSAcK IDNot Available
Chemspider ID141175
KEGG Compound IDC04823
BioCyc IDP-RIBOSYL-4-SUCCCARB-AMINOIMIDAZOLE
BiGG ID44624
Wikipedia LinkPhosphoribosylaminoimidazolesuccinocarboxamide
METLIN ID5762
PubChem Compound160666
PDB IDNot Available
ChEBI ID18319
References
Synthesis ReferenceShaw, Gordon; Thomas, Peter S.; Patey, Carole A. H.; Thomas, Susan E. Purines, pyrimidines and imidazoles. Part 50. Inhibition of adenylosuccinate AMP-lyase no. 4.3.2.2. by derivatives of N-(5-amino-1-b-D-ribofuranosylimidazole-4-carbonyl)-L-aspartic acid 5'-phosphate (SAICAR) and virazole 5'-phosphate. Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1979), (6), 1415-24.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Kmoch S, Hartmannova H, Stiburkova B, Krijt J, Zikanova M, Sebesta I: Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients. Hum Mol Genet. 2000 Jun 12;9(10):1501-13. [PubMed:10888601 ]
  2. Race V, Marie S, Vincent MF, Van den Berghe G: Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency. Hum Mol Genet. 2000 Sep 1;9(14):2159-65. [PubMed:10958654 ]
  3. Wevers RA, Engelke UF, Moolenaar SH, Brautigam C, de Jong JG, Duran R, de Abreu RA, van Gennip AH: 1H-NMR spectroscopy of body fluids: inborn errors of purine and pyrimidine metabolism. Clin Chem. 1999 Apr;45(4):539-48. [PubMed:10102915 ]
  4. Marinaki AM, Champion M, Kurian MA, Simmonds HA, Marie S, Vincent MF, van den Berghe G, Duley JA, Fairbanks LD: Adenylosuccinate lyase deficiency--first British case. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1231-3. [PubMed:15571235 ]
  5. Laikind PK, Seegmiller JE, Gruber HE: Detection of 5'-phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole in urine by use of the Bratton-Marshall reaction: identification of patients deficient in adenylosuccinate lyase activity. Anal Biochem. 1986 Jul;156(1):81-90. [PubMed:3740420 ]
  6. Zikanova M, Krijt J, Hartmannova H, Kmoch S: Preparation of 5-amino-4-imidazole-N-succinocarboxamide ribotide, 5-amino-4-imidazole-N-succinocarboxamide riboside and succinyladenosine, compounds usable in diagnosis and research of adenylosuccinate lyase deficiency. J Inherit Metab Dis. 2005;28(4):493-9. [PubMed:15902552 ]
  7. Keller KE, Tan IS, Lee YS: SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions. Science. 2012 Nov 23;338(6110):1069-72. doi: 10.1126/science.1224409. Epub 2012 Oct 18. [PubMed:23086999 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
ADSL
Uniprot ID:
P30566
Molecular weight:
54888.735
Reactions
SAICAR → Fumaric acid + AICARdetails
SAICAR → Fumaric acid + AICARdetails
General function:
Involved in phosphoribosylaminoimidazole carboxylase activity
Specific function:
Not Available
Gene Name:
PAICS
Uniprot ID:
P22234
Molecular weight:
47078.82
Reactions
Adenosine triphosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-Aspartic acid → ADP + Phosphoric acid + SAICARdetails
Adenosine triphosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-Aspartic acid → ADP + Phosphoric acid + SAICARdetails