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Record Information

Version

5.0

Status

Detected and Quantified

Creation Date

2006-08-13 04:36:31 UTC

Update Date

2023-02-21 17:16:49 UTC

HMDB ID

HMDB0003771

Secondary Accession Numbers

HMDB0029172
HMDB03771
HMDB29172

Metabolite Identification

Common Name

2-Methylacetoacetic acid

Description

2-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

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

View in JSmol View NMR Assignments View Stereo Labels

Synonyms

Value	Source
2-Methylacetoacetate	Generator
2-Methyl-3-oxo-butyric acid	HMDB
2-Methyl-3-oxo-butyrate	HMDB
2Methyl-3-ketovalerate	HMDB
(+/-)-2-methyl-3-oxobutanoate	HMDB
(+/-)-2-methyl-3-oxobutanoic acid	HMDB
2-Acetylpropionic acid	HMDB
2-Methyl-3-ketobutyric acid	HMDB
2-Methyl-3-oxo-butanoate	HMDB
2-Methyl-3-oxo-butanoic acid	HMDB
2-Methyl-3-oxobutanoate	HMDB
2-Methyl-3-oxobutanoic acid	HMDB
2-Methyl-3-oxobutyric acid	HMDB
2-Methyl-acetoacetic acid	HMDB
3-oxo-2-Methylbutyric acid	HMDB
a-Methylacetoacetic acid	HMDB
alpha-Methylacetoacetate	HMDB
alpha-Methylacetoacetic acid	HMDB
(-)-2-Methyl-3-oxobutanoic acid	HMDB
(2S)-2-Methyl-3-oxobutanoic acid	HMDB
(S)-2-Acetylpropionic acid	HMDB
(S)-2-Methyl-3-oxobutyric acid	HMDB
(±)-2-methyl-3-oxobutanoic acid	HMDB
3-Keto-2-methylbutyrate	HMDB
3-Keto-2-methylbutyric acid	HMDB
Α-methylacetoacetic acid	HMDB
2-Methylacetoacetic acid	HMDB

Chemical Formula

C₅H₈O₃

Average Molecular Weight

116.116

Monoisotopic Molecular Weight

116.047344118

IUPAC Name

(2R)-2-methyl-3-oxobutanoic acid

Traditional Name

(2R)-2-methyl-3-oxobutanoic acid

CAS Registry Number

76652-88-5

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 Key

GCXJINGJZAOJHR-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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Keto acids and derivatives

Sub Class

Short-chain keto acids and derivatives

Direct Parent

Short-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 Framework

Aliphatic acyclic compounds

External Descriptors

Not Available

Ontology

Physiological effect

Not Available

Disposition

Biological location

Cellular substructure

Non-excretory biofluid

Biofluid or Excreta

Blood (HMDB: HMDB0003771)

Excreta

Biofluid or Excreta

Urine (PMID: 4812006)

Source

Endogenous

Endogenous (HMDB: HMDB0003771)

Greylag goose (FooDB: FOOD00368)
Guinea hen (FooDB: FOOD00373)
Ostrich (FooDB: FOOD00422)
Velvet duck (FooDB: FOOD00427)
Pheasant (FooDB: FOOD00430)
Squab (FooDB: FOOD00481)
Turkey (FooDB: FOOD00494)
Quail (FooDB: FOOD00541)
Anatidae (FooDB: FOOD00576)
Rock ptarmigan (FooDB: FOOD00597)
Columbidae (Dove, Pigeon) (FooDB: FOOD00610)
Chicken (FooDB: FOOD00329)
Mallard duck (FooDB: FOOD00353)
Emu (FooDB: FOOD00360)

Equine

Horse (FooDB: FOOD00378)

Lagomorph

Ovis

Sheep (Mutton, Lamb) (FooDB: FOOD00473)

Bovine

Venison

Deer (FooDB: FOOD00524)
Mule deer (FooDB: FOOD00348)
Elk (FooDB: FOOD00359)

Caprae

Domestic goat (FooDB: FOOD00529)

Swine

Domestic pig (FooDB: FOOD00536)
Wild boar (FooDB: FOOD00307)

Process

Naturally occurring process

Biological process

Biochemical pathway

Disease pathway

Beta-Ketothiolase Deficiency (HMDB: HMDB0003771)

Role

Biological role

Nutrient (HMDB: HMDB0003771)

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular Properties

Property	Value	Source
Water Solubility	94.9 g/L	ALOGPS
logP	0.2	ALOGPS
logP	0.54	ChemAxon
logS	-0.09	ALOGPS
pKa (Strongest Acidic)	4.17	ChemAxon
pKa (Strongest Basic)	-7.5	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	54.37 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	27.11 m³·mol⁻¹	ChemAxon
Polarizability	11.03 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DeepCCS	[M+H]+	121.066	30932474
DeepCCS	[M-H]-	117.398	30932474
DeepCCS	[M-2H]-	154.652	30932474
DeepCCS	[M+Na]+	129.729	30932474

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
2-Methylacetoacetic acid	C[C@H](C(C)=O)C(O)=O	1885.2	Standard polar	33892256
2-Methylacetoacetic acid	C[C@H](C(C)=O)C(O)=O	917.9	Standard non polar	33892256
2-Methylacetoacetic acid	C[C@H](C(C)=O)C(O)=O	1019.3	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
2-Methylacetoacetic acid,1TMS,isomer #1	CC(=O)[C@@H](C)C(=O)O[Si](C)(C)C	1079.1	Semi standard non polar	33892256
2-Methylacetoacetic acid,1TMS,isomer #2	CC(O[Si](C)(C)C)=C(C)C(=O)O	1183.9	Semi standard non polar	33892256
2-Methylacetoacetic acid,1TMS,isomer #3	C=C(O[Si](C)(C)C)[C@@H](C)C(=O)O	1152.7	Semi standard non polar	33892256
2-Methylacetoacetic acid,2TMS,isomer #1	CC(O[Si](C)(C)C)=C(C)C(=O)O[Si](C)(C)C	1302.1	Semi standard non polar	33892256
2-Methylacetoacetic acid,2TMS,isomer #1	CC(O[Si](C)(C)C)=C(C)C(=O)O[Si](C)(C)C	1269.3	Standard non polar	33892256
2-Methylacetoacetic acid,2TMS,isomer #1	CC(O[Si](C)(C)C)=C(C)C(=O)O[Si](C)(C)C	1263.4	Standard polar	33892256
2-Methylacetoacetic acid,2TMS,isomer #2	C=C(O[Si](C)(C)C)[C@@H](C)C(=O)O[Si](C)(C)C	1208.4	Semi standard non polar	33892256
2-Methylacetoacetic acid,2TMS,isomer #2	C=C(O[Si](C)(C)C)[C@@H](C)C(=O)O[Si](C)(C)C	1209.5	Standard non polar	33892256
2-Methylacetoacetic acid,2TMS,isomer #2	C=C(O[Si](C)(C)C)[C@@H](C)C(=O)O[Si](C)(C)C	1295.7	Standard polar	33892256
2-Methylacetoacetic acid,1TBDMS,isomer #1	CC(=O)[C@@H](C)C(=O)O[Si](C)(C)C(C)(C)C	1286.2	Semi standard non polar	33892256
2-Methylacetoacetic acid,1TBDMS,isomer #2	CC(O[Si](C)(C)C(C)(C)C)=C(C)C(=O)O	1412.2	Semi standard non polar	33892256
2-Methylacetoacetic acid,1TBDMS,isomer #3	C=C(O[Si](C)(C)C(C)(C)C)[C@@H](C)C(=O)O	1355.6	Semi standard non polar	33892256
2-Methylacetoacetic acid,2TBDMS,isomer #1	CC(O[Si](C)(C)C(C)(C)C)=C(C)C(=O)O[Si](C)(C)C(C)(C)C	1693.1	Semi standard non polar	33892256
2-Methylacetoacetic acid,2TBDMS,isomer #1	CC(O[Si](C)(C)C(C)(C)C)=C(C)C(=O)O[Si](C)(C)C(C)(C)C	1701.8	Standard non polar	33892256
2-Methylacetoacetic acid,2TBDMS,isomer #1	CC(O[Si](C)(C)C(C)(C)C)=C(C)C(=O)O[Si](C)(C)C(C)(C)C	1600.6	Standard polar	33892256
2-Methylacetoacetic acid,2TBDMS,isomer #2	C=C(O[Si](C)(C)C(C)(C)C)[C@@H](C)C(=O)O[Si](C)(C)C(C)(C)C	1637.9	Semi standard non polar	33892256
2-Methylacetoacetic acid,2TBDMS,isomer #2	C=C(O[Si](C)(C)C(C)(C)C)[C@@H](C)C(=O)O[Si](C)(C)C(C)(C)C	1650.7	Standard non polar	33892256
2-Methylacetoacetic acid,2TBDMS,isomer #2	C=C(O[Si](C)(C)C(C)(C)C)[C@@H](C)C(=O)O[Si](C)(C)C(C)(C)C	1611.6	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - 2-Methylacetoacetic acid GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 2-Methylacetoacetic acid 10V, Negative-QTOF	splash10-00di-9400000000-029357b4d051ca8d370b	2021-09-23	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 2-Methylacetoacetic acid 20V, Negative-QTOF	splash10-00xr-9200000000-cb7cd3ae60ff315dba28	2021-09-23	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 2-Methylacetoacetic acid 40V, Negative-QTOF	splash10-0596-9000000000-cac1829091f5bbdeb66d	2021-09-23	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 2-Methylacetoacetic acid 10V, Positive-QTOF	splash10-00di-9000000000-18cf6a17f1382fff422f	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 2-Methylacetoacetic acid 20V, Positive-QTOF	splash10-0006-9000000000-b2fd07a2dc6a8b0f23fb	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 2-Methylacetoacetic acid 40V, Positive-QTOF	splash10-0006-9000000000-d248d070f34b5db1faa0	2021-09-24	Wishart Lab	View Spectrum

NMR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Predicted 1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-24	Wishart Lab	View Spectrum

IR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M-H]-)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+H]+)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+Na]+)	2023-02-03	FELIX lab	View Spectrum

Biological Properties

Cellular Locations

Extracellular
Membrane

Biospecimen Locations

Blood
Urine

Tissue Locations

Not Available

Pathways

Not Available

Name	SMPDB/PathBank	KEGG

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Quantified	Not Available	Not Available	Normal	Not Available	details
Urine	Detected and Quantified	0 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	4812006	details
Urine	Detected and Quantified	<2 umol/mmol creatinine	Children (1 - 18 years old)	Both	Normal	BC Children's Hos...	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Bladder cancer	28157703	details
Urine	Detected and Quantified	8030 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Beta-ketothiolase deficiency	8930414	details
Urine	Detected and Quantified	3368 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Beta-ketothiolase deficiency	8930414	details
Urine	Detected and Quantified	325.0 (0.0-650.0) umol/mmol creatinine	Children (1-13 years old)	Both	Beta-Ketothiolase deficiency	MetaGene: Metabol...	details

Associated Disorders and Diseases

Disease References

Beta-ketothiolase deficiency
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 ] 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)

External Links

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

FDB023226

KNApSAcK ID

Not Available

Chemspider ID

24191898

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

Not Available

PubChem Compound

150996

PDB ID

Not Available

ChEBI ID

37079

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Middleton 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

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 ]
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 ]
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 ]
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 ]

Showing metabocard for 2-Methylacetoacetic acid (HMDB0003771)

MOL for HMDB0003771 (2-Methylacetoacetic acid)

3D MOL for HMDB0003771 (2-Methylacetoacetic acid)

3D SDF for HMDB0003771 (2-Methylacetoacetic acid)

3D-SDF for HMDB0003771 (2-Methylacetoacetic acid)

PDB for HMDB0003771 (2-Methylacetoacetic acid)

3D PDB for HMDB0003771 (2-Methylacetoacetic acid)

SMILES for HMDB0003771 (2-Methylacetoacetic acid)

INCHI for HMDB0003771 (2-Methylacetoacetic acid)

Structure for HMDB0003771 (2-Methylacetoacetic acid)

3D Structure for HMDB0003771 (2-Methylacetoacetic acid)

Predicted Collision Cross Sections

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

NMR Spectra

IR Spectra