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Record Information
Creation Date2014-08-29 06:51:12 UTC
Update Date2018-03-21 17:46:21 UTC
Accession NumberT3D4425
Common NameAlpha-ketoisovaleric acid
ClassSmall Molecule
Descriptionalpha-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.
Compound Type
  • Animal Toxin
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
2-Keto-3-Methylbutyric acid
2-Ketoisovaleric acid
2-Ketoisvaleric acid
2-Oxo-3-methylbutanoic acid
2-Oxo-3-methylbutyric acid
2-Oxoisovaleric acid
3-Methyl-2-oxo-Butanoic acid
3-Methyl-2-oxo-Butyric acid
3-Methyl-2-oxobutanoic acid
3-Methyl-2-oxobutinoic acid
3-Methyl-2-oxobutyric acid
a-Keto-b-Methylbutyric acid
a-Keto-Isovaleric acid
a-Ketoisovaleric acid
a-Oxo-b-methylbutyric acid
a-Oxoisovaleric acid
alpha-Keto-beta-Methylbutyric acid
alpha-Keto-Isovaleric acid
Alpha-Ketoisovaleric acid
alpha-Ketoisovaleric acid
alpha-Oxo-beta-methylbutyric acid
alpha-Oxoisovaleric acid
Dimethylpyruvic acid
Isopropylglyoxylic acid
α-Ketoisovaleric acid
Chemical FormulaC5H8O3
Average Molecular Mass116.115 g/mol
Monoisotopic Mass116.047 g/mol
CAS Registry Number759-05-7
IUPAC Name3-methyl-2-oxobutanoic acid
Traditional Nameα-ketoisovalerate
InChI IdentifierInChI=1S/C5H8O3/c1-3(2)4(6)5(7)8/h3H,1-2H3,(H,7,8)
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
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • Most Tissues
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 Point31.5°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
Water Solubility30.2 g/LALOGPS
pKa (Strongest Acidic)3.37ChemAxon
pKa (Strongest Basic)-9.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity27.19 m³·mol⁻¹ChemAxon
Polarizability11.04 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) (Non-derivatized)splash10-000i-9500000000-ff936b879a69b5d118f8JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000i-8920000000-e37b37d64d43dcf763f0JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-000i-9400000000-e3995acc4818a98d0f48JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-0f79-9720000000-5d89487273e44ea61a68JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-000i-9700000000-209c737dcac7df2b198cJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0f79-5920000000-759a2f01b4f52767ade2JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-9500000000-ff936b879a69b5d118f8JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-8920000000-e37b37d64d43dcf763f0JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-000i-9400000000-e3995acc4818a98d0f48JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0f79-9720000000-5d89487273e44ea61a68JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-7900000000-7e325567183fb56996d5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0ufr-0930000000-be90b06add7135b4a539JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00dl-9000000000-52f9d8fc8386e4c512feJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-006x-9600000000-52aefdc997dac92c8459JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-9000000000-10ab58a33e9ca7dbace0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-000i-9000000000-ad51ff01c94b6046ad64JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-014i-0900000000-9993174a7b1801b90ddbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-00xr-9500000000-293818b81e0879b6feb2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-00di-9000000000-75058f27a2178b9cf121JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0006-9000000000-4c20af39e8ee009d5278JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-014i-0900000000-9993174a7b1801b90ddbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00xr-9500000000-1a58c6a6b4f5477dabddJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-75058f27a2178b9cf121JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-9000000000-cc4465a47e663be66df5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , negativesplash10-00di-9100000000-19511890852fce513a02JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00r2-9400000000-21f8c3fae79161c82099JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dl-9000000000-5f25e41413738bb6b5d7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-801af00dea93fcfd637dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-01b9-8900000000-5185c7dfc72c25069904JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00xs-9200000000-7e2a275a65197f96f5d7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0600-9000000000-0013e0ff06f9896a1337JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
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 alpha-ketoisovaleric acid are associated with Maple Syrup Urine Disease.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB04074
PubChem Compound ID49
ChemSpider ID48
UniProt IDNot Available
ChEBI ID16530
CTD IDNot Available
Stitch IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
Synthesis ReferenceNot Available
General References
  1. 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. [2089249 ]
  2. 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. [2026685 ]
  3. Livesey G, Lund P: Binding of branched-chain 2-oxo acids to bovine serum albumin. Biochem J. 1982 Apr 15;204(1):265-72. [7115325 ]
  4. 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. [6422161 ]
  5. 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. [6895847 ]
  6. 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. [9869358 ]
  7. 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. [5096137 ]
  8. 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. [6393856 ]
  9. 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. [6581765 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available


General Function:
L-valine transaminase 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:
Uniprot ID:
Molecular Weight:
44287.445 Da
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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. [17016423 ]