3-Methylglutaconic acid (T3D4265)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationXML
Record Information
Version2.0
Creation Date2014-08-29 06:10:05 UTC
Update Date2018-03-21 17:46:13 UTC
Accession NumberT3D4265
Identification
Common Name3-Methylglutaconic acid
ClassSmall Molecule
Description3-Methylglutaconic acid is an intermediate (as the CoA thioester) in the leucine degradative pathway as well as the mevalonate shunt, a pathway that links isoprenoid metabolism with mitochondrial acetyl-CoA metabolism (PMID: 7603789). 3-methylglutaconyl-CoA hydratase is involved in the metabolism process of 3-methylglutaconic acid. When present in sufficiently high levels, 3-methylglutaconic acid can act as an acidogen and a metabotoxin. 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. Chronically high levels of 3-methylglutaconic acid are associated with at least five inborn errors of metabolism including 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-methylglutaconic aciduria type I, 3-methylglutaconic aciduria type III, 3-methylglutaconic aciduria type IV, and guanidinoacetate methyltransferase deficiency (GAMT deficiency). 3-Methylglutaconic acid is an organic acid. 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 the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.
Compound Type
  • Animal Toxin
  • Ester
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
3-Methylglutaconate
b-Methylglutaconate
b-Methylglutaconic acid
beta-Methylglutaconate
beta-Methylglutaconic acid
Chemical FormulaC6H8O4
Average Molecular Mass144.125 g/mol
Monoisotopic Mass144.042 g/mol
CAS Registry Number5746-90-7
IUPAC Name(2E)-3-methylpent-2-enedioic acid
Traditional Nameβ-methylglutaconic acid
SMILES[H]\C(C(O)=O)=C(\C)CC(O)=O
InChI IdentifierInChI=1S/C6H8O4/c1-4(2-5(7)8)3-6(9)10/h2H,3H2,1H3,(H,7,8)(H,9,10)/b4-2+
InChI KeyInChIKey=WKRBKYFIJPGYQC-DUXPYHPUSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as methyl-branched fatty acids. These are fatty acids with an acyl chain that has a methyl branch. Usually, they are saturated and contain only one or more methyl group. However, branches other than methyl may be present.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentMethyl-branched fatty acids
Alternative Parents
Substituents
  • Methyl-branched fatty acid
  • Unsaturated fatty acid
  • Dicarboxylic 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 Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencySMP00138 Not Available
3-Methylglutaconic Aciduria Type ISMP00139 Not Available
3-Methylglutaconic Aciduria Type IIISMP00140 Not Available
3-Methylglutaconic Aciduria Type IVSMP00141 Not Available
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)SMP00188 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 Solubility8.69 g/LALOGPS
logP0.37ALOGPS
logP0.29ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)3.85ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity33.51 m³·mol⁻¹ChemAxon
Polarizability13.27 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, Positivesplash10-0015-9200000000-ff306cede85d252e0d4c2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00di-9340000000-0b493822a103307b8f662017-10-06View 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 (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_2_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-000f-9000000000-fa6952af79fc3b2759fe2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-0a4j-9000000000-3a5a017393a0592a65ff2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-000f-9000000000-14ef6163925508d3f6662021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-0002-9000000000-ada755597943f74819c42021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-0002-9000000000-70f10348ac9e844187652021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-5a9ee69bdb3960321fa62021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002b-2900000000-b6862aeffb1aa9fae1d02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-9300000000-7ab01dfb0b86abdac8172016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-3692ceff17a888ae88362016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-5900000000-dc4d4a80a164f3fd1fea2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0007-8900000000-7ece848c8011e4a202002016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a7l-9300000000-8b54483c15a17429b9f82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-9200000000-70569e6181007374644c2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000t-9000000000-9426c88487da5c337c1b2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000x-9000000000-60467181d27d878d6aca2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-9400000000-79724b8b1198fb4429492021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001j-9000000000-4f399595435fe16b38802021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001c-9000000000-1ee161ce72a30f1b08142021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-18View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityAccumulation of 3-methylglutaconic acid in the body has been shown to be toxic. 3-methylglutaconyl-CoA hydratase is involved in the metabolism process of 3-methylglutaconic acid. 3-Methylglutaconic acid accumulates in patients with a deficiency of this enzyme and a large amount of 3-methylglutaconic acid appear in urine. (Wikipedia).
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 3-methylglutaconic acid are associated with at least 5 inborn errors of metabolism including: 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency, 3-Methylglutaconic Aciduria Type I, 3-Methylglutaconic Aciduria Type III, 3-Methylglutaconic Aciduria Type IV and Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency).
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00522
PubChem Compound ID1551553
ChEMBL IDCHEMBL1401952
ChemSpider ID1267861
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID37245
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia Link3-Methylglutaconic acid
References
Synthesis ReferenceAoyama, Takayuki; Kato, Kazuo; Shimada, Nobuyoshi; Fujii, Akio; Takita, Tomohisa. Production of 3-methylglutaconic acid. Jpn. Kokai Tokkyo Koho (1986), 3 pp.
MSDSNot Available
General References
  1. Kelley RI, Kratz L: 3-methylglutaconic acidemia in Smith-Lemli-Opitz syndrome. Pediatr Res. 1995 May;37(5):671-4. [7603789 ]
  2. Mitchell GA, Jakobs C, Gibson KM, Robert MF, Burlina A, Dionisi-Vici C, Dallaire L: Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. Prenat Diagn. 1995 Aug;15(8):725-9. [7479590 ]
  3. Holme E, Greter J, Jacobson CE, Larsson NG, Lindstedt S, Nilsson KO, Oldfors A, Tulinius M: Mitochondrial ATP-synthase deficiency in a child with 3-methylglutaconic aciduria. Pediatr Res. 1992 Dec;32(6):731-5. [1287564 ]
  4. Costeff H, Elpeleg O, Apter N, Divry P, Gadoth N: 3-Methylglutaconic aciduria in "optic atrophy plus". Ann Neurol. 1993 Jan;33(1):103-4. [8494328 ]
  5. Sheffer RN, Zlotogora J, Elpeleg ON, Raz J, Ben-Ezra D: Behr's syndrome and 3-methylglutaconic aciduria. Am J Ophthalmol. 1992 Oct 15;114(4):494-7. [1384336 ]
  6. Kelley RI: Quantification of 3-methylglutaconic acid in urine, plasma, and amniotic fluid by isotope-dilution gas chromatography/mass spectrometry. Clin Chim Acta. 1993 Nov 15;220(2):157-64. [8111960 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available