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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (8)transporters (3) Show 11 proteins XML

enzymes (8)transporters (3) Show 11 proteins

Record Information

Version

5.0

Status

Detected and Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2020-10-09 20:57:01 UTC

HMDB ID

HMDB0000019

Secondary Accession Numbers

HMDB00019
HMDB0004260
HMDB04260

Metabolite Identification

Common Name

alpha-Ketoisovaleric acid

Description

alpha-Ketoisovaleric acid is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids. alpha-Ketoisovaleric acid is a neurotoxin, an acidogen, and a metabotoxin. A neurotoxin causes damage to nerve cells and nerve tissues. 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 alpha-ketoisovaleric acid are associated with maple syrup urine disease. MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine. The symptoms of MSUD often show in infancy and lead to severe brain damage if untreated. MSUD may also present later depending on the severity of the disease. If left untreated in older individuals, during times of metabolic crisis, symptoms of the condition include uncharacteristically inappropriate, extreme, or erratic behaviour and moods, hallucinations, anorexia, weight loss, anemia, diarrhea, vomiting, dehydration, lethargy, oscillating hypertonia and hypotonia, ataxia, seizures, hypoglycemia, ketoacidosis, opisthotonus, pancreatitis, rapid neurological decline, and coma. In maple syrup urine disease, the brain concentration of branched-chain ketoacids can increase 10- to 20-fold. This leads to a depletion of glutamate and a consequent reduction in the concentration of brain glutamine, aspartate, alanine, and other amino acids. The result is a compromise of energy metabolism because of a failure of the malate-aspartate shuttle and a diminished rate of protein synthesis (PMID: 15930465 ). alpha-Ketoisovaleric acid 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 MSUD. Many affected children with organic acidemias experience intellectual disability or delayed development.

Structure

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

COMPND    https://cactus.nci.nih.gov/chemical/structure/CC(C)C(=O)C(O)=O/file?format=sd... 
AUTHOR    GENERATED BY OPEN BABEL 3.1.0
HETATM    1  C   UNL     1       1.726  -1.109  -0.995  1.00  0.00           C  
HETATM    2  C   UNL     1       1.255  -0.398   0.274  1.00  0.00           C  
HETATM    3  C   UNL     1       2.363   0.528   0.781  1.00  0.00           C  
HETATM    4  C   UNL     1       0.023   0.415  -0.033  1.00  0.00           C  
HETATM    5  O   UNL     1       0.131   1.562  -0.394  1.00  0.00           O  
HETATM    6  C   UNL     1      -1.328  -0.198   0.108  1.00  0.00           C  
HETATM    7  O   UNL     1      -2.428   0.527  -0.166  1.00  0.00           O  
HETATM    8  O   UNL     1      -1.437  -1.351   0.470  1.00  0.00           O  
HETATM    9  H   UNL     1       2.617  -1.697  -0.773  1.00  0.00           H  
HETATM   10  H   UNL     1       0.937  -1.769  -1.357  1.00  0.00           H  
HETATM   11  H   UNL     1       1.961  -0.370  -1.761  1.00  0.00           H  
HETATM   12  H   UNL     1       1.021  -1.137   1.040  1.00  0.00           H  
HETATM   13  H   UNL     1       2.597   1.268   0.016  1.00  0.00           H  
HETATM   14  H   UNL     1       2.027   1.035   1.686  1.00  0.00           H  
HETATM   15  H   UNL     1       3.254  -0.060   1.004  1.00  0.00           H  
HETATM   16  H   UNL     1      -3.282   0.087  -0.060  1.00  0.00           H  
CONECT    1    2    9   10   11                                       
CONECT    2    1    3    4   12                                       
CONECT    3    2   13   14   15                                       
CONECT    4    2    5    5    6                                       
CONECT    5    4    4                                                 
CONECT    6    4    7    8    8                                       
CONECT    7    6   16                                                 
CONECT    8    6    6                                                 
CONECT    9    1                                                      
CONECT   10    1                                                      
CONECT   11    1                                                      
CONECT   12    2                                                      
CONECT   13    3                                                      
CONECT   14    3                                                      
CONECT   15    3                                                      
CONECT   16    7                                                      
MASTER        0    0    0    0    0    0    0    0   16    0   16    0
END

View in JSmol View Stereo Labels

Synonyms

Value	Source
2-Keto-3-methylbutyric acid	ChEBI
2-Ketoisovaleric acid	ChEBI
2-Ketovaline	ChEBI
2-oxo-3-Methylbutanoic acid	ChEBI
2-oxo-3-Methylbutyric acid	ChEBI
2-Oxoisovaleric acid	ChEBI
3-Methyl-2-oxobutanoate	ChEBI
3-Methyl-2-oxobutyric acid	ChEBI
alpha-Keto-isovaleric acid	ChEBI
alpha-Ketovaline	ChEBI
alpha-oxo-beta-Methylbutyricacid	ChEBI
alpha-Oxoisovaleric acid	ChEBI
Dimethylpyruvic acid	ChEBI
Isopropylglyoxylic acid	ChEBI
2-oxo-3-Methylbutanoate	Kegg
2-Oxoisovalerate	Kegg
2-Oxoisopentanoate	Kegg
2-Keto-3-methylbutyrate	Generator
2-Ketoisovalerate	Generator
2-oxo-3-Methylbutyrate	Generator
3-Methyl-2-oxobutanoic acid	Generator
3-Methyl-2-oxobutyrate	Generator
a-Keto-isovalerate	Generator
a-Keto-isovaleric acid	Generator
alpha-Keto-isovalerate	Generator
Α-keto-isovalerate	Generator
Α-keto-isovaleric acid	Generator
a-Ketovaline	Generator
Α-ketovaline	Generator
a-oxo-b-Methylbutyricacid	Generator
Α-oxo-β-methylbutyricacid	Generator
a-Oxoisovalerate	Generator
a-Oxoisovaleric acid	Generator
alpha-Oxoisovalerate	Generator
Α-oxoisovalerate	Generator
Α-oxoisovaleric acid	Generator
Dimethylpyruvate	Generator
Isopropylglyoxylate	Generator
2-Oxoisopentanoic acid	Generator
a-Ketoisovalerate	Generator
a-Ketoisovaleric acid	Generator
alpha-Ketoisovalerate	Generator
Α-ketoisovalerate	Generator
Α-ketoisovaleric acid	Generator
2-Ketoisvaleric acid	HMDB
2-oxo-3-Methyl-butyrate	HMDB
3-Methyl-2-oxo-butanoate	HMDB
3-Methyl-2-oxo-butanoic acid	HMDB
3-Methyl-2-oxo-butyrate	HMDB
3-Methyl-2-oxo-butyric acid	HMDB
3-Methyl-2-oxobutinoate	HMDB
3-Methyl-2-oxobutinoic acid	HMDB
a-Keto-b-methylbutyrate	HMDB
a-Keto-b-methylbutyric acid	HMDB
a-oxo-b-Methylbutyrate	HMDB
a-oxo-b-Methylbutyric acid	HMDB
alpha-Keto-beta-methylbutyrate	HMDB
alpha-Keto-beta-methylbutyric acid	HMDB
alpha-oxo-beta-Methylbutyrate	HMDB
alpha-oxo-beta-Methylbutyric acid	HMDB
Ketovaline	HMDB
alpha-Ketoisopentanoic acid	HMDB
alpha-Ketoisovaleric acid	Generator, MeSH

Chemical Formula

C₅H₈O₃

Average Molecular Weight

116.1152

Monoisotopic Molecular Weight

116.047344122

IUPAC Name

3-methyl-2-oxobutanoic acid

Traditional Name

α-ketoisovalerate

CAS Registry Number

759-05-7

SMILES

CC(C)C(=O)C(O)=O

InChI Identifier

InChI=1S/C5H8O3/c1-3(2)4(6)5(7)8/h3H,1-2H3,(H,7,8)

InChI Key

QHKABHOOEWYVLI-UHFFFAOYSA-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

Branched fatty acid
Methyl-branched fatty acid
Short-chain keto acid
Alpha-keto acid
Fatty acyl
Alpha-hydroxy ketone
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

2-oxo monocarboxylic acid (CHEBI:16530 )
Branched fatty acids (C00141 )
Branched fatty acids (LMFA01020274 )

Ontology

Disposition

Route of exposure:

Enteral:

Ingestion

Source:

Biological:

Animal

Plant:

Biological location:

Tissue and substructures:

Placenta

Biofluid and excreta:

Subcellular:

Cell and elements:

Extracellular

Process

Naturally occurring process:

Biological process:

Cellular process:

Cell signaling

Biochemical pathway:

Valine, Leucine and Isoleucine Degradation

Role

Indirect biological role:

Biological role:

Industrial application:

Pharmaceutical industry:

Pharmaceutical

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	31.5 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	30.2 g/L	ALOGPS
logP	0.49	ALOGPS
logP	1.31	ChemAxon
logS	-0.59	ALOGPS
pKa (Strongest Acidic)	3.37	ChemAxon
pKa (Strongest Basic)	-9.7	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	27.19 m³·mol⁻¹	ChemAxon
Polarizability	11.04 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

Spectra

GC-MS

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000i-9500000000-ff936b879a69b5d118f8	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000i-8920000000-e37b37d64d43dcf763f0	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)	splash10-000i-9400000000-e3995acc4818a98d0f48	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)	splash10-0f79-9720000000-5d89487273e44ea61a68	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-000i-9700000000-209c737dcac7df2b198c	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0f79-5920000000-759a2f01b4f52767ade2	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-9500000000-ff936b879a69b5d118f8	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-8920000000-e37b37d64d43dcf763f0	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-000i-9400000000-e3995acc4818a98d0f48	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0f79-9720000000-5d89487273e44ea61a68	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-7900000000-7e325567183fb56996d5	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0ufr-0930000000-be90b06add7135b4a539	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00dl-9000000000-52f9d8fc8386e4c512fe	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-006x-9600000000-52aefdc997dac92c8459	2017-10-06	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00dl-9000000000-c2360354892d35d7ea05	2021-09-05	View Spectrum

LC-MS/MS

Spectrum Type	Description	Splash Key	Deposition Date	View
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-000i-9000000000-10ab58a33e9ca7dbace0	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-000i-9000000000-ad51ff01c94b6046ad64	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-014i-0900000000-9993174a7b1801b90ddb	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-00xr-9500000000-293818b81e0879b6feb2	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-00di-9000000000-75058f27a2178b9cf121	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-0006-9000000000-4c20af39e8ee009d5278	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-014i-0900000000-9993174a7b1801b90ddb	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-00xr-9500000000-1a58c6a6b4f5477dabdd	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-00di-9000000000-75058f27a2178b9cf121	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0006-9000000000-cc4465a47e663be66df5	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , negative	splash10-00di-9100000000-19511890852fce513a02	2017-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00r2-9400000000-21f8c3fae79161c82099	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00dl-9000000000-5f25e41413738bb6b5d7	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-801af00dea93fcfd637d	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-01b9-8900000000-5185c7dfc72c25069904	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00xs-9200000000-7e2a275a65197f96f5d7	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0600-9000000000-0013e0ff06f9896a1337	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-006x-9000000000-733fb7227d2d053b112f	2021-09-07	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-006x-9000000000-3d71962a24e475d7c256	2021-09-07	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-7d7dba214bf92b0376ad	2021-09-07	View Spectrum

NMR

Spectrum Type	Description	Deposition Date	View
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, D₂O, experimental)	2016-10-22	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, D₂O, experimental)	2016-10-22	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-16	View Spectrum
2D NMR	[¹H, ¹³C] NMR Spectrum (2D, 600 MHz, H₂O, predicted)	2012-12-04	View Spectrum
2D NMR	[¹H, ¹H] 2D NMR Spectrum (predicted)	2012-12-04	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm
Extracellular
Membrane
Mitochondria

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Saliva
Urine

Tissue Locations

Placenta

Pathways

Name	SMPDB/Pathwhiz	KEGG
Valine, Leucine and Isoleucine Degradation
Beta-Ketothiolase Deficiency		Not Available
2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency		Not Available
Propionic Acidemia		Not Available
3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected and Quantified	14.0 (0.0-28.0) uM	Children (1-13 years old)	Both	Normal	8412012	details
Blood	Detected and Quantified	11.0 +/- 1.7 uM	Adult (>18 years old)	Both	Normal	Geigy Scientific ...	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Female	Normal	27355821	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	6 +/- 3 uM	Adult (>18 years old)	Both	Normal	18502700	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	8.2 +/- 6.8 uM	Adult (>18 years old)	Both	Normal	8412012	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	27543620	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	18052033	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	29808030	details
Saliva	Detected and Quantified	0.679 +/- 0.369 uM	Adult (>18 years old)	Female	Normal	Sugimoto et al. (...	details
Saliva	Detected and Quantified	0.752 +/- 0.287 uM	Adult (>18 years old)	Not Specified	Normal	Sugimoto et al. (...	details
Saliva	Detected and Quantified	1.06 +/- 0.436 uM	Adult (>18 years old)	Not Specified	Normal	Sugimoto et al. (...	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected and Quantified	0.345 +/- 0.858 uM	Adult (>18 years old)	Male	Normal	Sugimoto et al. (...	details
Saliva	Detected and Quantified	0.434 +/- 0.382 uM	Adult (>18 years old)	Female	Normal	Sugimoto et al. (...	details
Saliva	Detected and Quantified	0.656 +/- 0.399 uM	Adult (>18 years old)	Female	Normal	Sugimoto et al. (...	details
Urine	Detected and Quantified	0.78-1.2 umol/mmol creatinine	Adult (>18 years old)	Female	Normal	27012787	details
Urine	Detected and Quantified	0.16 +/- 0.48 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	2026685	details
Urine	Detected and Quantified	0.5 (0.2-1.1) umol/mmol creatinine	Adult (>18 years old)	Both	Normal	24023812	details
Urine	Detected and Quantified	0.13 (0.00-0.54) umol/mmol creatinine	Adult (>18 years old)	Male	Normal	9869358	details
Urine	Detected and Quantified	0.07 (0.01-0.45) umol/mmol creatinine	Adult (>18 years old)	Female	Normal	5096137	details
Urine	Detected and Quantified	0.79-1.1 umol/mmol creatinine	Adult (>18 years old)	Male	Normal	27012787	details
Urine	Detected and Quantified	0.07 (0.01-0.45) umol/mmol creatinine	Adult (>18 years old)	Female	Normal	9869358	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected and Quantified	10.7 +/- 5.5 uM	Adult (>18 years old)	Both	Heart Transplant	21359215	details
Blood	Detected and Quantified	237 uM	Children (1-13 years old)	Female	Maple syrup urine disease	Peritoneal dialys...	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	189 uM	Children (1-13 years old)	Female	Maple syrup urine disease	Peritoneal dialys...	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal Cancer	27275383	details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Bladder cancer	28157703	details
Urine	Detected and Quantified	550.00 (300.00-800.00) umol/mmol creatinine	Adult (>18 years old)	Both	Maple syrup urine disease (MSUD). When treated, the concentrations are 1-2 uM/mM.	MetaGene: Metabol...	details
Urine	Detected and Quantified	550.00 (300.00-800.00) umol/mmol creatinine	Children (1-13 years old)	Both	Maple syrup urine disease (MSUD). When treated, the concentrations are 1-2 uM/mM.	MetaGene: Metabol...	details

Associated Disorders and Diseases

Disease References

Colorectal cancer
Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ]
Maple syrup urine disease
G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium. Wendel, U., Becker, K., Przyrembel, H. et al. (1980). Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids. Eur J Pediatr (1980) 134: 57. https://doi.org/10.1007/BF00442404. Eur J Pediatr.

Associated OMIM IDs

114500 (Colorectal cancer)
248600 (Maple syrup urine disease)

External Links

DrugBank ID

DB04074

Phenol Explorer Compound ID

Not Available

FooDB ID

FDB012250

KNApSAcK ID

C00007623

Chemspider ID

KEGG Compound ID

C00141

BioCyc ID

2-KETO-ISOVALERATE

BiGG ID

34011

Wikipedia Link

Alpha-Ketoisovaleric acid

METLIN ID

5091

PubChem Compound

PDB ID

Not Available

ChEBI ID

16530

Food Biomarker Ontology

Not Available

VMH ID

3MOB

MarkerDB ID

MDB00000009

References

Synthesis Reference

Pirrung, Michael C.; Ha, Hyun Joon; Holmes, Christopher P. Purification and inhibition of spinach a,b-dihydroxyacid dehydratase . Journal of Organic Chemistry (1989), 54(7), 1543-8.

Material Safety Data Sheet (MSDS)

Download (PDF)

General References

Schaefer K, von Herrath D, Erley CM, Asmus G: Calcium ketovaline as new therapy for uremic hyperphosphatemia. Miner Electrolyte Metab. 1990;16(6):362-4. [PubMed:2089249 ]
Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. [PubMed:2026685 ]
Livesey G, Lund P: Binding of branched-chain 2-oxo acids to bovine serum albumin. Biochem J. 1982 Apr 15;204(1):265-72. [PubMed:7115325 ]
Shigematsu Y, Kikuchi K, Momoi T, Sudo M, Kikawa Y, Nosaka K, Kuriyama M, Haruki S, Sanada K, Hamano N, et al.: Organic acids and branched-chain amino acids in body fluids before and after multiple exchange transfusions in maple syrup urine disease. J Inherit Metab Dis. 1983;6(4):183-9. [PubMed:6422161 ]
Chuang DT, Niu WL, Cox RP: Activities of branched-chain 2-oxo acid dehydrogenase and its components in skin fibroblasts from normal and classical-maple-syrup-urine-disease subjects. Biochem J. 1981 Oct 15;200(1):59-67. [PubMed:6895847 ]
Lee SH, Kim SO, Chung BC: Gas chromatographic-mass spectrometric determination of urinary oxoacids using O-(2,3,4,5,6-pentafluorobenzyl)oxime-trimethylsilyl ester derivatization and cation-exchange chromatography. J Chromatogr B Biomed Sci Appl. 1998 Nov 20;719(1-2):1-7. [PubMed:9869358 ]
Gallina DL, Dominguez JM, Hoschoian JC, Barrio JR: Maintenance of nitrogen balance in a young woman by substitution of -ketoisovaleric acid for valine. J Nutr. 1971 Sep;101(9):1165-7. [PubMed:5096137 ]
Schauder P, Schroder K, Langenbeck U: Serum branched-chain amino and keto acid response to a protein-rich meal in man. Ann Nutr Metab. 1984;28(6):350-6. [PubMed:6393856 ]
Tsuchiya H, Hashizume I, Tokunaga T, Tatsumi M, Takagi N, Hayashi T: High-performance liquid chromatography of alpha-keto acids in human saliva. Arch Oral Biol. 1983;28(11):989-92. [PubMed:6581765 ]
Yudkoff M, Daikhin Y, Nissim I, Horyn O, Luhovyy B, Lazarow A, Nissim I: Brain amino acid requirements and toxicity: the example of leucine. J Nutr. 2005 Jun;135(6 Suppl):1531S-8S. [PubMed:15930465 ]
Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

Only showing the first 10 proteins. There are 11 proteins in total.

Show all enzymes and transporters

Enzymes

Enzyme Details

1. Pyruvate dehydrogenase E1 component subunit beta, mitochondrial

General function:: Involved in catalytic activity
Specific function:: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:: PDHB
Uniprot ID:: P11177
Molecular weight:: 39233.1

References

Jackson RH, Singer TP: Inactivation of the 2-ketoglutarate and pyruvate dehydrogenase complexes of beef heart by branched chain keto acids. J Biol Chem. 1983 Feb 10;258(3):1857-65. [PubMed:6822537 ]

Enzyme Details

2. Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

General function:: Involved in oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
Specific function:: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:: PDHA1
Uniprot ID:: P08559
Molecular weight:: 43295.255

References

Jackson RH, Singer TP: Inactivation of the 2-ketoglutarate and pyruvate dehydrogenase complexes of beef heart by branched chain keto acids. J Biol Chem. 1983 Feb 10;258(3):1857-65. [PubMed:6822537 ]

Enzyme Details

3. Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial

General function:: Involved in oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
Specific function:: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:: PDHA2
Uniprot ID:: P29803
Molecular weight:: 42932.855

References

Jackson RH, Singer TP: Inactivation of the 2-ketoglutarate and pyruvate dehydrogenase complexes of beef heart by branched chain keto acids. J Biol Chem. 1983 Feb 10;258(3):1857-65. [PubMed:6822537 ]

Enzyme Details

4. Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial

General function:: Involved in acyltransferase activity
Specific function:: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:: DLAT
Uniprot ID:: P10515
Molecular weight:: 68996.03

References

Jackson RH, Singer TP: Inactivation of the 2-ketoglutarate and pyruvate dehydrogenase complexes of beef heart by branched chain keto acids. J Biol Chem. 1983 Feb 10;258(3):1857-65. [PubMed:6822537 ]

Enzyme Details

5. 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial

General function:: Involved in catalytic activity
Specific function:: The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).
Gene Name:: BCKDHB
Uniprot ID:: P21953
Molecular weight:: 43122.065

Reactions

alpha-Ketoisovaleric acid + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine → [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO(2)	details
alpha-Ketoisovaleric acid + Thiamine pyrophosphate → 2-Methyl-1-hydroxypropyl-ThPP + Carbon dioxide	details

Enzyme Details

6. 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial

General function:: Involved in oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
Specific function:: The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).
Gene Name:: BCKDHA
Uniprot ID:: P12694
Molecular weight:: 50470.58

Reactions

alpha-Ketoisovaleric acid + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine → [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO(2)	details
alpha-Ketoisovaleric acid + Thiamine pyrophosphate → 2-Methyl-1-hydroxypropyl-ThPP + Carbon dioxide	details

Enzyme Details

7. Branched-chain-amino-acid aminotransferase, cytosolic

General function:: Involved in catalytic activity
Specific function:: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.
Gene Name:: BCAT1
Uniprot ID:: P54687
Molecular weight:: 38644.77

Reactions

L-Valine + Oxoglutaric acid → alpha-Ketoisovaleric acid + L-Glutamic acid	details

Enzyme Details

8. Branched-chain-amino-acid aminotransferase, mitochondrial

General function:: Involved in catalytic activity
Specific function:: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
Gene Name:: BCAT2
Uniprot ID:: O15382
Molecular weight:: 33776.315

Reactions

L-Valine + Oxoglutaric acid → alpha-Ketoisovaleric acid + L-Glutamic acid	details

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]

Transporters

Enzyme Details

1. Monocarboxylate transporter 4

General function:: Involved in transmembrane transport
Specific function:: Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate
Gene Name:: SLC16A3
Uniprot ID:: O15427
Molecular weight:: 49468.9

References

Manning Fox JE, Meredith D, Halestrap AP: Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol. 2000 Dec 1;529 Pt 2:285-93. [PubMed:11101640 ]

Enzyme Details

2. Monocarboxylate transporter 1

General function:: Involved in transmembrane transport
Specific function:: Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate
Gene Name:: SLC16A1
Uniprot ID:: P53985
Molecular weight:: 53957.7

References

Broer S, Schneider HP, Broer A, Rahman B, Hamprecht B, Deitmer JW: Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J. 1998 Jul 1;333 ( Pt 1):167-74. [PubMed:9639576 ]

Enzyme Details

3. Monocarboxylate transporter 2

General function:: Involved in transmembrane transport
Specific function:: Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. MCT2 is a high affinity pyruvate transporter
Gene Name:: SLC16A7
Uniprot ID:: O60669
Molecular weight:: 52185.7

References

Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. [PubMed:10417314 ]

Only showing the first 10 proteins. There are 11 proteins in total.

Show all enzymes and transporters

Showing metabocard for alpha-Ketoisovaleric acid (HMDB0000019)

MOL for HMDB0000019 (alpha-Ketoisovaleric acid)

3D MOL for HMDB0000019 (alpha-Ketoisovaleric acid)

3D SDF for HMDB0000019 (alpha-Ketoisovaleric acid)

3D-SDF for HMDB0000019 (alpha-Ketoisovaleric acid)

PDB for HMDB0000019 (alpha-Ketoisovaleric acid)

3D PDB for HMDB0000019 (alpha-Ketoisovaleric acid)

SMILES for HMDB0000019 (alpha-Ketoisovaleric acid)

INCHI for HMDB0000019 (alpha-Ketoisovaleric acid)

Structure for HMDB0000019 (alpha-Ketoisovaleric acid)

3D Structure for HMDB0000019 (alpha-Ketoisovaleric acid)

GC-MS

LC-MS/MS

NMR

Enzymes

References

References

References

References

Reactions

Reactions

Reactions

Reactions

References

Transporters

References

References

References