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Record Information
Creation Date2014-08-29 06:51:12 UTC
Update Date2018-03-21 17:46:21 UTC
Accession NumberT3D4424
Common Name3-Methyl-2-oxovaleric acid
ClassSmall Molecule
Description3-Methyl-2-oxovaleric acid is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids. 3-Methyl-2-oxovaleric 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 3-methyl-2-oxovaleric 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). 3-Methyl-2-oxovaleric 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.
Compound Type
  • Animal Toxin
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
(3R)-3-Methyl-2-oxopentanoic acid
(R)-3-methyl-2-oxopentanoic acid
(S)-3-methyl-2-oxopentanoic acid
2-Keto-3-methylvaleric acid
2-Oxo-3-methyl-N-valeric acid
2-Oxo-3-methylpentanoic acid
2-Oxo-3-methylvaleric acid
2-Oxokolavenic acid
3-Methyl-2-oxo-pentanoic acid
3-Methyl-2-oxo-Valeric acid
3-Methyl-2-oxopentanoic acid
a-Keto-b-Methyl-N-valeric acid
a-Keto-b-methylvaleric acid
a-Oxo-b-methyl-N-valeric acid
a-Oxo-b-methylvaleric acid
alpha-Keto-beta-Methyl-N-valeric acid
alpha-Keto-beta-methylvaleric acid
alpha-Oxo-beta-methyl-N-valeric acid
alpha-Oxo-beta-methylvaleric acid
Chemical FormulaC6H10O3
Average Molecular Mass130.142 g/mol
Monoisotopic Mass130.063 g/mol
CAS Registry Number1460-34-0
IUPAC Name3-methyl-2-oxopentanoic acid
Traditional Name3-methyl-2-oxopentanoic acid
InChI IdentifierInChI=1/C6H10O3/c1-3-4(2)5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9)
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
  • 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 FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Prostate
Valine, Leucine and Isoleucine DegradationSMP00032 map00280
Maple Syrup Urine DiseaseSMP00199 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
AppearanceWhite powder.
Experimental Properties
Melting PointNot Available
Boiling PointNot Available
Solubility915.5 mg/mL
LogPNot Available
Predicted Properties
Water Solubility9.86 g/LALOGPS
pKa (Strongest Acidic)3.52ChemAxon
pKa (Strongest Basic)-9.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity31.79 m³·mol⁻¹ChemAxon
Polarizability13.09 ųChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-000i-9610000000-d2ffd4c2796688c555eeJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-000i-9720000000-9cbc934e100bedd87f17JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000i-9720000000-5acbdc73aee24c023763JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000i-6930000000-8c2cf1d8df538010611bJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-000i-6930000000-7bef6751c4c607393e5eJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0hg9-4950000000-3e1c700a6f553bf63afbJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-9610000000-d2ffd4c2796688c555eeJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-9720000000-9cbc934e100bedd87f17JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-9720000000-5acbdc73aee24c023763JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-6930000000-8c2cf1d8df538010611bJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-056r-9000000000-d08073312b337cdae9e6JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-05bo-9400000000-9937bff65302162dc3b9JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000w-9300000000-0a6ff60455403c38be39JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0002-9000000000-7ee6d2fb63c6ea4cccfaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-002b-9000000000-47d18dff23b741029581JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-0900000000-ae9da2a9acfa56fc6091JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , negativesplash10-004r-5900000000-a3f740a5c859439255beJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-06sr-7900000000-4920c1aefcca814ec1f6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4r-9100000000-16995fa8eb603d828a2fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-a6ccc899039a438533aeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004r-5900000000-50107933abbe9c175553JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ri-9700000000-23998218af9ee2898594JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-a30461e2df45eeb8f795JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of Toxicity3-Methyl-2-oxovaleric acid is produced from isoleucine by cytosolic branched chain aminotransferase 1, whereupon it is further degraded by branched chain keto acid dehydrogenase E1 to 2-methyl-1-hydroxybutyl-ThPP. It is used as a clinical marker for maple syrup urine disease (MSUD). MSUD is caused by a deficiency of the branched-chain -keto acid dehydrogenase complex resulting in an accumulation of branched-chain amino acids and the corresponding -keto-and -hydroxy acids in blood, urine and cerebrospinal fluid causing neurological damage and mental retardation.
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-methyl-2-oxovaleric acid are associated with Maple Syrup Urine Disease.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
PubChem Compound ID47
ChEMBL IDNot Available
ChemSpider ID46
UniProt IDNot Available
ChEBI ID35932
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
Synthesis ReferenceKondo, Shigeo; Sudo, Tetsuji; Ogiwara, Mitsuo; Takeuchi, Hiroshi. a-Oxo-b-methyl-n-valeric acid and its salts. Jpn. Kokai Tokkyo Koho (1979), 3 pp.
General References
  1. Wendel U, Even G, Langenbeck U, Schadewaldt P, Hummel W: Determination of (S)- and (R)-2-oxo-3-methylvaleric acid in plasma of patients with maple syrup urine disease. Clin Chim Acta. 1992 Jun 15;208(1-2):85-91. [1638756 ]
  2. Przyrembel H, Bremer HJ, Duran M, Bruinvis L, Ketting D, Wadman SK, Baumgartner R, Irle U, Bachmann C: Propionyl-CoA carboxylase deficiency with overflow of metabolites of isoleucine catabolism at all levels. Eur J Pediatr. 1979 Jan 18;130(1):1-14. [759179 ]
  3. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available