Succinylacetone (T3D4471)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-08-29 06:51:36 UTC
Update Date2018-03-21 17:46:20 UTC
Accession NumberT3D4471
Identification
Common NameSuccinylacetone
ClassSmall Molecule
DescriptionSuccinylacetone, also known as 4,6-dioxoheptanoic acid or SUAC, belongs to the class of compounds known as medium-chain keto acids and derivatives. These are keto acids with 6 to 12 carbon atoms. Succinylacetone is soluble (in water) and a weakly acidic compound (based on its pKa). Succinylacetone has been detected in amniotic fluid, blood, and urine. Within the cell, succinylacetone is primarily located in the cytoplasm (predicted from logP). Succinylacetone can be created by the oxidation of glycine, and is a precursor of methylglyoxal (Wikipedia). Succinylacetone is an abnormal tyrosine metabolite that arises from defects in the enzyme called fumarylacetoacetase (PMID: 16448836). Fumarylacetoacetase normally catalyzes the hydrolysis of 4-fumarylacetoacetate into fumarate and acetoacetate. If present in sufficiently high levels, succinylacetone can act as an acidogen, an oncometabolite, and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. An oncometabolite is an endogenous metabolite that causes cancer. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of succinylacetone are associated with tyrosinemia type I. Type I tyrosinemia is an inherited metabolism disorder due to a shortage of the enzyme fumarylacetoacetate hydrolase that is needed to break down tyrosine. Patients usually develop features such as hepatic necrosis, renal tubular injury, and hypertrophic cardiomyopathy. Neurologic and dermatologic manifestations are also possible. The urine has an odour of cabbage or rancid butter. Succinylacetone is a keto-acid, which is a subclass of organic acids. 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 tyrosinemia. Many affected children with organic acidemias experience intellectual disability or delayed development. Succinylacetone appears to function as an oncometabolite (similar in function to succinate, another oncometabolite) as patients with high levels of this compound often develop hepatocellular carcinoma (PMID: 20003495).
Compound Type
  • Animal Toxin
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
4,6-Dioxoheptanoate
4,6-Dioxoheptanoic acid
Chemical FormulaC7H10O4
Average Molecular Mass158.152 g/mol
Monoisotopic Mass158.058 g/mol
CAS Registry Number51568-18-4
IUPAC Name4,6-dioxoheptanoic acid
Traditional Namesuccinylacetone
SMILESCC(=O)CC(=O)CCC(O)=O
InChI IdentifierInChI=1S/C7H10O4/c1-5(8)4-6(9)2-3-7(10)11/h2-4H2,1H3,(H,10,11)
InChI KeyInChIKey=WYEPBHZLDUPIOD-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as medium-chain keto acids and derivatives. These are keto acids with a 6 to 12 carbon atoms long side chain.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassKeto acids and derivatives
Sub ClassMedium-chain keto acids and derivatives
Direct ParentMedium-chain keto acids and derivatives
Alternative Parents
Substituents
  • Medium-chain keto acid
  • Gamma-keto acid
  • 1,3-diketone
  • 1,3-dicarbonyl compound
  • Ketone
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Tyrosinemia Type ISMP00218 Not Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point66 - 67°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility24.1 g/LALOGPS
logP-0.18ALOGPS
logP0.15ChemAxon
logS-0.82ALOGPS
pKa (Strongest Acidic)4.15ChemAxon
pKa (Strongest Basic)-7.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.44 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity36.98 m³·mol⁻¹ChemAxon
Polarizability15.07 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
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, Positivesplash10-000f-9200000000-418fe15f4a3ff86cd7322017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00dl-9510000000-9b8725af310299084be02017-10-06View 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_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 (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_5) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0a4i-0900000000-bc1ed64644f1d5262a672012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4l-4900000000-4a799061d93a46eb98ab2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-1900000000-bb8ea63020dfb2d73fd62012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0fdy-9000000000-d000e19711c34e043ab92021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0002-9000000000-60a15fc8627ad96e85322021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0002-9400000000-d9f2cde762a2868297c32021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0a59-9000000000-0c4c76b64acd6d49029a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-03c08ce11d1bfc6939ac2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0002-9100000000-940ff687b04afbb690852021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-006x-1900000000-78eabe7ae2f320bd578f2015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0kml-7900000000-db14b02751e17fac33232015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9100000000-b6e51a674fbdfbbe701a2015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1900000000-cfd9bc7542d69961cfde2015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4r-5900000000-3abd8a41f7a1bab5e9a22015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9200000000-63209abdb7044cb484b22015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-9600000000-e6fe2f0606f1545e63f82021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0601-9300000000-f4da7f3a1baacd6285c22021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-9a962f60cab056b14ceb2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-9500000000-8ab84079b41abee332012021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0007-9000000000-4c7d97bda3ec2644c3b02021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052f-9000000000-1b9dad08fc2bac65faee2021-09-24View Spectrum
MSMass Spectrum (Electron Ionization)splash10-000f-9100000000-a3b92f310030718acb912014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, 5%_DMSO, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 100 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, 200 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, 300 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, 400 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, 500 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, 600 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, 700 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, 800 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, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View 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 succinylacetone are associated with Tyrosinemia Type I.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00635
PubChem Compound ID5312
ChEMBL IDCHEMBL222824
ChemSpider ID5121
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDSHU
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis Reference Levenson, Corey H. Process for the preparation of succinylacetone. PCT Int. Appl. (1991), 9 pp.
MSDSLink
General References
  1. Magera MJ, Gunawardena ND, Hahn SH, Tortorelli S, Mitchell GA, Goodman SI, Rinaldo P, Matern D: Quantitative determination of succinylacetone in dried blood spots for newborn screening of tyrosinemia type I. Mol Genet Metab. 2006 May;88(1):16-21. Epub 2006 Jan 31. [16448836 ]
  2. Laberge C, Lescault A, Grenier A, Morrisette J, Gagne R, Gadbois P, Halket J: Oral loading of homogentisic acid in controls and in obligate heterozygotes for hereditary tyrosinemia type I. Am J Hum Genet. 1990 Aug;47(2):329-37. [2378359 ]
  3. Poudrier J, Lettre F, St-Louis M, Tanguay RM: Genotyping of a case of tyrosinaemia type I with normal level of succinylacetone in amniotic fluid. Prenat Diagn. 1999 Jan;19(1):61-3. [10073910 ]
  4. Jakobs C, Dorland L, Wikkerink B, Kok RM, de Jong AP, Wadman SK: Stable isotope dilution analysis of succinylacetone using electron capture negative ion mass fragmentography: an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I. Clin Chim Acta. 1988 Feb 15;171(2-3):223-31. [3286060 ]
  5. Fernandez-Canon JM, Baetscher MW, Finegold M, Burlingame T, Gibson KM, Grompe M: Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione-dependent nonenzymatic bypass in tyrosine catabolism. Mol Cell Biol. 2002 Jul;22(13):4943-51. [12052898 ]
  6. Kimura A, Endo F, Kagimoto S, Inoue T, Suzuki M, Kurosawa T, Tohma M, Fujisawa T, Kato H: Tyrosinemia type I-like disease: a possible manifestation of 3-oxo-delta 4-steroid 5 beta-reductase deficiency. Acta Paediatr Jpn. 1998 Jun;40(3):211-7. [9695292 ]
  7. Endo F, Katoh H, Yamamoto S, Matsuda I: A murine model for type III tyrosinemia: lack of immunologically detectable 4-hydroxyphenylpyruvic acid dioxygenase enzyme protein in a novel mouse strain with hypertyrosinemia. Am J Hum Genet. 1991 Apr;48(4):704-9. [2014797 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Egl nine homolog 1
General Function:
Peptidyl-proline dioxygenase activity
Specific Function:
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.
Gene Name:
EGLN1
Uniprot ID:
Q9GZT9
Molecular Weight:
46020.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5018 uMNot AvailableBindingDB 50197063
References
  1. Mecinovic J, Loenarz C, Chowdhury R, Schofield CJ: 2-Oxoglutarate analogue inhibitors of prolyl hydroxylase domain 2. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6192-5. doi: 10.1016/j.bmcl.2009.09.005. Epub 2009 Sep 6. [19775891 ]