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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2019-07-23 05:44:15 UTC
HMDB IDHMDB0000522
Secondary Accession Numbers
  • HMDB00522
Metabolite Identification
Common Name3-Methylglutaconic acid
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.
Structure
Data?1563860655
Synonyms
ValueSource
3-MethylglutaconateGenerator
b-MethylglutaconateHMDB
b-Methylglutaconic acidHMDB
beta-MethylglutaconateHMDB
beta-Methylglutaconic acidHMDB
Β-methylglutaconic acidHMDB
3-Methyl-2-pentenedioic acidHMDB
3E-MethylglutaconateHMDB
3-Methylglutaconic acidHMDB, MeSH
Chemical FormulaC6H8O4
Average Molecular Weight144.1253
Monoisotopic Molecular Weight144.042258744
IUPAC Name(2E)-3-methylpent-2-enedioic acid
Traditional Nameβ-methylglutaconic acid
CAS Registry Number5746-90-7
SMILES
C\C(CC(O)=O)=C/C(O)=O
InChI Identifier
InChI=1S/C6H8O4/c1-4(2-5(7)8)3-6(9)10/h2H,3H2,1H3,(H,7,8)(H,9,10)/b4-2+
InChI KeyWKRBKYFIJPGYQC-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
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Indirect biological role:

Industrial application:

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 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
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0015-9200000000-ff306cede85d252e0d4cJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00di-9340000000-0b493822a103307b8f66JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002b-2900000000-b6862aeffb1aa9fae1d0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-9300000000-7ab01dfb0b86abdac817JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-3692ceff17a888ae8836JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-5900000000-dc4d4a80a164f3fd1feaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0007-8900000000-7ece848c8011e4a20200JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a7l-9300000000-8b54483c15a17429b9f8JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biospecimen Locations
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified<10 uMAdult (>18 years old)FemaleNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified<6 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected and Quantified<10 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified<20 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified<1500 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified<25 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified1.0 - 6.5 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified<6 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified<12.42 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified<25 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified<12 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected and Quantified<20 umol/mmol creatinineInfant (0-1 year old)Not SpecifiedNormal details
UrineDetected and Quantified<0.0200 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified6.2 (2.8-8.3) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified10.707 +/- 4.243 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified7.5 (3.4-9.5) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified15.86 +/- 6.052 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified125 uMAdult (>18 years old)Female3-methylglutaconic aciduria type I details
UrineDetected and Quantified20-488 umol/mmol creatinineChildren (1-13 years old)BothSengers syndrome details
UrineDetected and Quantified750.0 (500.0-1000.0) umol/mmol creatinineChildren (1-13 years old)Both3-Methylglutaconic Aciduria (TYPE I)
    • MetaGene: Metabol...
details
UrineDetected and Quantified0-230 umol/mmol creatinineInfant (0-1 year old)Male3-methylglutaconic aciduria type II, X-linked details
UrineDetected and Quantified16-68 umol/mmol creatinineAdolescent (13-18 years old)Female3-Methylglutaconic Aciduria (Type IV) details
UrineDetected and Quantified4-200 umol/mmol creatinineChildren (1-13 years old)Both3-Methylglutaconic Aciduria (Type IV) details
UrineDetected and Quantified13000 umol/mmol creatinineChildren (1-13 years old)Male3-Methylglutaconic Aciduria (Type V) details
UrineDetected and Quantified3714 umol/mmol creatinineAdult (>18 years old)Female3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency details
UrineDetected and Quantified32-51 umol/mmol creatinineAdult (>18 years old)Female3-methylglutaconic aciduria type I details
UrineDetected and Quantified62-90 umol/mmol creatinineAdult (>18 years old)Female3-methylglutaconic aciduria type I details
UrineDetected and Quantified4166.4 umol/mmol creatinineNewborn (0-30 days old)Male3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency details
UrineDetected and Quantified3714 umol/mmol creatinineAdult (>18 years old)Female3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency details
UrineDetected and Quantified29-109 umol/mmol creatinineChildren (1-13 years old)Female3-Methylglutaconic Aciduria (Type VII) details
UrineDetected and Quantified34-160 umol/mmol creatinineAdolescent (13-18 years old)Female3-Methylglutaconic Aciduria (Type VII) details
UrineDetected and Quantified52-93 umol/mmol creatinineInfant (0-1 year old)Female3-Methylglutaconic Aciduria (Type VII) details
UrineDetected and Quantified0.0160-0.196 umol/mmol creatinineChildren (1-13 years old)Female3-Methylglutaconic Aciduria (Type VI) details
UrineDetected and Quantified94-141 umol/mmol creatinineAdult (>18 years old)Not Specified
3-Methylglutaconic Aciduria (TYPE I)
details
UrineDetected and Quantified570 umol/mmol creatinineChildren (1-13 years old)Not Specified3-Methylglutaconic Aciduria (TYPE I) details
UrineDetected and Quantified10.714 +/- 4.929 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified12.053 +/- 6.469 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
UrineDetected and Quantified14.626 +/- 7.998 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified4.5 (0.00-9.0) umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
    • MetaGene: Metabol...
details
UrineDetected and Quantified17.038 +/- 8.547 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
UrineDetected and Quantified5070.0 (140.0-10000.0) umol/mmol creatinineChildren (1-13 years old)Both3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
    • MetaGene: Metabol...
details
Associated Disorders and Diseases
Disease References
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
  1. Bischof F, Nagele T, Wanders RJ, Trefz FK, Melms A: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an adult with leukoencephalopathy. Ann Neurol. 2004 Nov;56(5):727-30. [PubMed:15505778 ]
  2. Santarelli F, Cassanello M, Enea A, Poma F, D'Onofrio V, Guala G, Garrone G, Puccinelli P, Caruso U, Porta F, Spada M: A neonatal case of 3-hydroxy-3-methylglutaric-coenzyme A lyase deficiency. Ital J Pediatr. 2013 May 24;39:33. doi: 10.1186/1824-7288-39-33. [PubMed:23705938 ]
  3. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
3-Methylglutaconic aciduria type I
  1. Engelke UF, Kremer B, Kluijtmans LA, van der Graaf M, Morava E, Loupatty FJ, Wanders RJ, Moskau D, Loss S, van den Bergh E, Wevers RA: NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism. NMR Biomed. 2006 Apr;19(2):271-8. [PubMed:16541463 ]
  2. Wortmann SB, Kremer BH, Graham A, Willemsen MA, Loupatty FJ, Hogg SL, Engelke UF, Kluijtmans LA, Wanders RJ, Illsinger S, Wilcken B, Cruysberg JR, Das AM, Morava E, Wevers RA: 3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy. Neurology. 2010 Sep 21;75(12):1079-83. doi: 10.1212/WNL.0b013e3181f39a8a. [PubMed:20855850 ]
  3. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Eosinophilic esophagitis
  1. (). Mordechai, Hien, and David S. Wishart. .
3-methylglutaconic aciduria type II, X-linked
  1. Cantlay AM, Shokrollahi K, Allen JT, Lunt PW, Newbury-Ecob RA, Steward CG: Genetic analysis of the G4.5 gene in families with suspected Barth syndrome. J Pediatr. 1999 Sep;135(3):311-5. [PubMed:10484795 ]
3-Methylglutaconic Aciduria type VI
  1. Wortmann S, Rodenburg RJ, Huizing M, Loupatty FJ, de Koning T, Kluijtmans LA, Engelke U, Wevers R, Smeitink JA, Morava E: Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation. Mol Genet Metab. 2006 May;88(1):47-52. doi: 10.1016/j.ymgme.2006.01.013. Epub 2006 Mar 9. [PubMed:16527507 ]
3-Methylglutaconic Aciduria type IV
  1. Wortmann SB, Rodenburg RJ, Jonckheere A, de Vries MC, Huizing M, Heldt K, van den Heuvel LP, Wendel U, Kluijtmans LA, Engelke UF, Wevers RA, Smeitink JA, Morava E: Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy. Brain. 2009 Jan;132(Pt 1):136-46. doi: 10.1093/brain/awn296. Epub 2008 Nov 16. [PubMed:19015156 ]
3-Methylglutaconic Aciduria type V
  1. Ojala T, Polinati P, Manninen T, Hiippala A, Rajantie J, Karikoski R, Suomalainen A, Tyni T: New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies. Pediatr Res. 2012 Oct;72(4):432-7. doi: 10.1038/pr.2012.92. Epub 2012 Jul 13. [PubMed:22797137 ]
3-Methylglutaconic aciduria type VII
  1. Wortmann SB, Zietkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, Muntau AC, Rakovic A, Renkema GH, Rodenburg RJ, Strom TM, Meitinger T, Rubio-Gozalbo ME, Chrusciel E, Distelmaier F, Golzio C, Jansen JH, van Karnebeek C, Lillquist Y, Lucke T, Ounap K, Zordania R, Yaplito-Lee J, van Bokhoven H, Spelbrink JN, Vaz FM, Pras-Raves M, Ploski R, Pronicka E, Klein C, Willemsen MA, de Brouwer AP, Prokisch H, Katsanis N, Wevers RA: CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am J Hum Genet. 2015 Feb 5;96(2):245-57. doi: 10.1016/j.ajhg.2014.12.013. Epub 2015 Jan 15. [PubMed:25597510 ]
Sengers syndrome
  1. Di Rosa G, Deodato F, Loupatty FJ, Rizzo C, Carrozzo R, Santorelli FM, Boenzi S, D'Amico A, Tozzi G, Bertini E, Maiorana A, Wanders RJ, Dionisi-Vici C: Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: a novel subtype of 3-methylglutaconic aciduria. J Inherit Metab Dis. 2006 Aug;29(4):546-50. doi: 10.1007/s10545-006-0279-y. Epub 2006 May 30. [PubMed:16736096 ]
Associated OMIM IDs
  • 246450 (3-Hydroxy-3-methylglutaryl-CoA lyase deficiency)
  • 250950 (3-Methylglutaconic aciduria type I)
  • 610247 (Eosinophilic esophagitis)
  • 302060 (3-methylglutaconic aciduria type II, X-linked)
  • 614739 (3-Methylglutaconic Aciduria type VI)
  • 250951 (3-Methylglutaconic Aciduria type IV)
  • 610198 (3-Methylglutaconic Aciduria type V)
  • 616271 (3-Methylglutaconic aciduria type VII)
  • 212350 (Sengers syndrome)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022090
KNApSAcK IDNot Available
Chemspider ID1267861
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia Link3-Methylglutaconic acid
METLIN ID5507
PubChem Compound1551553
PDB IDNot Available
ChEBI ID37245
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceAoyama, Takayuki; Kato, Kazuo; Shimada, Nobuyoshi; Fujii, Akio; Takita, Tomohisa. Production of 3-methylglutaconic acid. Jpn. Kokai Tokkyo Koho (1986), 3 pp.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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. [PubMed:7479590 ]
  2. 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. [PubMed:1287564 ]
  3. 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. [PubMed:8494328 ]
  4. 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. [PubMed:1384336 ]
  5. 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. [PubMed:8111960 ]
  6. Kelley RI, Kratz L: 3-methylglutaconic acidemia in Smith-Lemli-Opitz syndrome. Pediatr Res. 1995 May;37(5):671-4. [PubMed:7603789 ]