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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2006-08-13 04:36:31 UTC
Update Date2023-02-21 17:16:49 UTC
HMDB IDHMDB0003771
Secondary Accession Numbers
  • HMDB0029172
  • HMDB03771
  • HMDB29172
Metabolite Identification
Common Name2-Methylacetoacetic acid
Description2-Methylacetoacetic acid (CAS: 2382-59-4) is a metabolite that has an increased excretion in patients with acetoacetyl-CoA thiolase (EC 2.3.1.9) deficiency (OMIM: 607809 , ACAT1; OMIM: 100678 , ACAT2; OMIM: 604770 , ACAA2; OMIM: 607809 ). Thiolases are ubiquitous and important enzymes. Several isoenzymes are known, which can occur in the cytosol (ACAT2), the mitochondria (ACAT1), or the peroxisomes (ACAA2). Thiolases are CoA-dependent enzymes which catalyze the formation of a carbon-carbon bond in a Claisen condensation step and its reverse reaction via a thiolytic degradation mechanism. Mitochondrial acetoacetyl-coenzyme A (CoA) thiolase (T2) is important in the pathways for the synthesis and degradation of ketone bodies as well as for the degradation of 2-methylacetoacetyl-CoA (PMID: 17371050 , 14518824 , 9744475 , 9001814 ). Moreover, 2-methylacetoacetic acid is found to be associated with beta-ketothiolase deficiency, which is also an inborn error of metabolism. 2-Methylacetoacetic acid is found in urine and can be used as a biomarker for the diagnosis of beta-ketothiolase deficiency.
Structure
Thumb
Synonyms
Chemical FormulaC5H8O3
Average Molecular Weight116.116
Monoisotopic Molecular Weight116.047344118
IUPAC Name(2R)-2-methyl-3-oxobutanoic acid
Traditional Name(2R)-2-methyl-3-oxobutanoic acid
CAS Registry Number76652-88-5
SMILES
C[C@H](C(C)=O)C(O)=O
InChI Identifier
InChI=1S/C5H8O3/c1-3(4(2)6)5(7)8/h3H,1-2H3,(H,7,8)/t3-/m1/s1
InChI KeyGCXJINGJZAOJHR-GSVOUGTGSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as short-chain keto acids and derivatives. These are keto acids with an alkyl chain the contains less than 6 carbon atoms.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassKeto acids and derivatives
Sub ClassShort-chain keto acids and derivatives
Direct ParentShort-chain keto acids and derivatives
Alternative Parents
Substituents
  • Beta-keto acid
  • Branched fatty acid
  • Methyl-branched fatty acid
  • Short-chain keto acid
  • Beta-hydroxy ketone
  • Fatty acyl
  • 1,3-dicarbonyl compound
  • Ketone
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organooxygen compound
  • Organic oxide
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Ontology
Physiological effectNot Available
Disposition
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
Predicted Chromatographic Properties
Spectra
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot Available
Normal
      Not Available
details
UrineDetected and Quantified0 umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified<2 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothBladder cancer details
UrineDetected and Quantified8030 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedBeta-ketothiolase deficiency details
UrineDetected and Quantified3368 umol/mmol creatinineChildren (1-13 years old)Not Specified
Beta-ketothiolase deficiency
details
UrineDetected and Quantified325.0 (0.0-650.0) umol/mmol creatinineChildren (1-13 years old)BothBeta-Ketothiolase deficiency
    • MetaGene: Metabol...
details
Associated Disorders and Diseases
Disease References
Beta-ketothiolase deficiency
  1. Fontaine M, Briand G, Ser N, Armelin I, Rolland MO, Degand P, Vamecq J: Metabolic studies in twin brothers with 2-methylacetoacetyl-CoA thiolase deficiency. Clin Chim Acta. 1996 Nov 15;255(1):67-83. [PubMed:8930414 ]
  2. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Associated OMIM IDs
  • 203750 (Beta-ketothiolase deficiency)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB023226
KNApSAcK IDNot Available
Chemspider ID24191898
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound40578931
PDB IDNot Available
ChEBI ID37079
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceMiddleton B; Bartlett K The synthesis and characterisation of 2-methylacetoacetyl coenzyme A and its use in the identification of the site of the defect in 2-methylacetoacetic and 2-methyl-3-hydroxybutyric aciduria. Clinica chimica acta; international journal of clinical chemistry (1983), 128(2-3), 291-305.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Haapalainen AM, Merilainen G, Pirila PL, Kondo N, Fukao T, Wierenga RK: Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. Biochemistry. 2007 Apr 10;46(14):4305-21. Epub 2007 Mar 20. [PubMed:17371050 ]
  2. Fukao T, Nakamura H, Song XQ, Nakamura K, Orii KE, Kohno Y, Kano M, Yamaguchi S, Hashimoto T, Orii T, Kondo N: Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency. Hum Mutat. 1998;12(4):245-54. [PubMed:9744475 ]
  3. Fukao T, Zhang GX, Sakura N, Kubo T, Yamaga H, Hazama A, Kohno Y, Matsuo N, Kondo M, Yamaguchi S, Shigematsu Y, Kondo N: The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles under stable conditions have subtle abnormalities in T2-deficient patients with some residual T2 activity. J Inherit Metab Dis. 2003;26(5):423-31. [PubMed:14518824 ]
  4. Fukao T, Kodama A, Aoyanagi N, Tsukino R, Uemura S, Song XQ, Watanebe H, Kuhara T, Matsumoto I, Orii T, Kondo N: Mild form of beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase deficiency) in two Japanese siblings: identification of detectable residual activity and cross-reactive material in EB-transformed lymphocytes. Clin Genet. 1996 Oct;50(4):263-6. [PubMed:9001814 ]