SAICAR (T3D4281)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-08-29 06:13:39 UTC
Update Date2018-03-21 17:46:15 UTC
Accession NumberT3D4281
Identification
Common NameSAICAR
ClassSmall Molecule
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.
Compound Type
  • Amine
  • Animal Toxin
  • Ether
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate
(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinic acid
(S)-2-(5-amino-1-(5-phospho-delta-ribosyl)imidazole-4-carboxamido)succinate
(S)-2-(5-amino-1-(5-phospho-delta-ribosyl)imidazole-4-carboxamido)succinic acid
(S)-2-[5-Amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
(S)-2-[5-Amino-1-(5-phospho-delta-ribosyl)imidazole-4-carboxamido]succinate
1-(5'-Phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole
1-(5'-Phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazole
1-(5'-Phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazole' 1-(5'-Phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole
5'-Phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazole
5'-Phosphoribosyl-4-(N-succinocarbozamide)-5-aminoimidazole
5-Amino-4-imidazole-N-succinocarboxamide ribonucleotide
L-N-[(5-Amino-1-b-D-ribofuranosylimidazol-4-yl)carbonyl]-5'-(dihydrogen phosphate)
L-N-[(5-Amino-1-beta-delta-ribofuranosylimidazol-4-yl)carbonyl]-5'-(dihydrogen phosphate)
N-(5-Amino-1-ribofuranosylimidazol-4-ylcarbonyl)aspartic acid 5'-phosphate
N-[5-Amino-1-(5'-phosphoribofuranosyl)-4-imidazolecarbonyl]aspartate
N-[5-Amino-1-(5'-phosphoribofuranosyl)-4-imidazolecarbonyl]aspartic acid
Phosphoribosylaminoimidazolesuccinocarboxamide
SAICAriboside
Succino-AICAR
Succinylaminoimidazole carboxamide riboside
Chemical FormulaC13H19N4O12P
Average Molecular Mass454.283 g/mol
Monoisotopic Mass454.074 g/mol
CAS Registry Number3031-95-6
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
SMILES[H][C@@](CC(O)=O)(N=C(O)C1=C(N)N(C=N1)[C@]1([H])O[C@]([H])(COP(O)(O)=O)[C@@]([H])(O)[C@@]1([H])O)C(O)=O
InChI IdentifierInChI=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 KeyInChIKey=NAQGHJTUZRHGAC-ZZZDFHIKSA-N
Chemical Taxonomy
Description 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
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Fibroblasts
  • Intestine
Pathways
NameSMPDB LinkKEGG Link
Purine MetabolismSMP00050 map00230
Adenylosuccinate Lyase DeficiencySMP00167 Not Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot 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 KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05n1-9732500000-f3a7f13b1dee5f81c7a82017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-05ot-9600116000-74a62efcb34072bbe3522017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_7) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_11) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_12) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_13) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_14) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_15) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-055o-1592600000-05db249dfb0f14143f9f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-3950000000-6ebf6a64483dd13927822016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001l-5940000000-e218e278f5195eb903412016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0ug3-6381900000-4fec69ff813fe652ea7d2016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004j-9350000000-e4e387627fbca1ef12012016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9100000000-95f6153e96335a5d2b322016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0f79-2012900000-f38ec5261c12799bc3542021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9022000000-a24939a2980b6834f5bc2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9110000000-7f66eadbb3c3527bbc8c2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0024900000-6f3c27fcd647c50d79d02021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0096-1293000000-d46017274b02e79e42772021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-3891000000-ed7da10b4a914197adb32021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of SAICAR are associated with Adenylosuccinate Lyase Deficiency.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00797
PubChem Compound ID160666
ChEMBL IDNot Available
ChemSpider ID141175
KEGG IDC04823
UniProt IDNot Available
OMIM ID
ChEBI ID18319
BioCyc IDP-RIBOSYL-4-SUCCCARB-AMINOIMIDAZOLE
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
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.
MSDSNot Available
General References
  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. [15571235 ]
  2. 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. [3740420 ]
  3. 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. [10958654 ]
  4. 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. [15902552 ]
  5. 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. [10888601 ]
  6. 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. [10102915 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Pyruvate kinase PKM
General Function:
Pyruvate kinase activity
Specific Function:
Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
Gene Name:
PKM
Uniprot ID:
P14618
Molecular Weight:
57936.38 Da
References
  1. 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. [23086999 ]