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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2015-03-09 23:54:16 UTC
HMDB IDHMDB00019
Secondary Accession Numbers
  • HMDB04260
Metabolite Identification
Common NameAlpha-ketoisovaleric acid
DescriptionAlpha-ketoisovaleric acid is a branched chain organic acid which is a precursor to leucine and valine synthesis. It is also a degradation product from valine. The enzyme dihydroxy-acid dehydratase catalyzes the fourth step in the biosynthesis of isoleucine and valine, through the dehydration of 2, 3-dihydroxy-isovaleic acid into alpha-ketoisovaleric acid.
Structure
Thumb
Synonyms
  1. 2-Keto-3-Methylbutyrate
  2. 2-Keto-3-Methylbutyric acid
  3. 2-Ketoisovalerate
  4. 2-Ketoisovaleric acid
  5. 2-Ketoisvaleric acid
  6. 2-Oxo-3-methyl-butyrate
  7. 2-Oxo-3-methylbutanoate
  8. 2-Oxo-3-methylbutanoic acid
  9. 2-Oxo-3-methylbutyrate
  10. 2-Oxo-3-methylbutyric acid
  11. 2-Oxoisovalerate
  12. 2-Oxoisovaleric acid
  13. 3-Methyl-2-oxo-Butanoate
  14. 3-Methyl-2-oxo-Butanoic acid
  15. 3-Methyl-2-oxo-Butyrate
  16. 3-Methyl-2-oxo-Butyric acid
  17. 3-Methyl-2-oxobutanoate
  18. 3-Methyl-2-oxobutanoic acid
  19. 3-Methyl-2-oxobutinoate
  20. 3-Methyl-2-oxobutinoic acid
  21. 3-Methyl-2-oxobutyrate
  22. 3-Methyl-2-oxobutyric acid
  23. a-Keto-b-Methylbutyrate
  24. a-Keto-b-Methylbutyric acid
  25. a-Keto-Isovalerate
  26. a-Keto-Isovaleric acid
  27. a-Ketoisovalerate
  28. a-Ketoisovaleric acid
  29. a-Oxo-b-methylbutyrate
  30. a-Oxo-b-methylbutyric acid
  31. a-Oxoisovalerate
  32. a-Oxoisovaleric acid
  33. alpha-Keto-beta-Methylbutyrate
  34. alpha-Keto-beta-Methylbutyric acid
  35. alpha-Keto-Isovalerate
  36. alpha-Keto-Isovaleric acid
  37. alpha-Ketoisovalerate
  38. alpha-Ketoisovaleric acid
  39. alpha-Oxo-beta-methylbutyrate
  40. alpha-Oxo-beta-methylbutyric acid
  41. alpha-Oxoisovalerate
  42. alpha-Oxoisovaleric acid
  43. Dimethylpyruvate
  44. Dimethylpyruvic acid
  45. Isopropylglyoxylate
  46. Isopropylglyoxylic acid
  47. Ketovaline
Chemical FormulaC5H8O3
Average Molecular Weight116.1152
Monoisotopic Molecular Weight116.047344122
IUPAC Name3-methyl-2-oxobutanoic acid
Traditional Nameα-ketoisovalerate
CAS Registry Number759-05-7
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 KeyQHKABHOOEWYVLI-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassLipids
ClassFatty Acids and Conjugates
Sub ClassBranched Fatty Acids
Other Descriptors
  • 2-oxo monocarboxylic acid(ChEBI)
  • Aliphatic Acyclic Compounds
  • Branched fatty acids(KEGG)
  • Branched fatty acids(Lipidmaps)
  • Organic Compounds
  • short-chain fatty acid(ChEBI)
  • straight-chain saturated fatty acid(ChEBI)
Substituents
  • Alpha Keto Acid
  • Carboxylic Acid
  • Ketone
  • Short Chain Keto Acid
Direct ParentBranched Fatty Acids
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Mitochondria
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point31.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility30.2ALOGPS
logP0.49ALOGPS
logP1.31ChemAxon
logS-0.59ALOGPS
pKa (Strongest Acidic)3.37ChemAxon
pKa (Strongest Basic)-9.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity27.19 m3·mol-1ChemAxon
Polarizability11.04 Å3ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Most Tissues
Pathways
NameSMPDB LinkKEGG Link
Valine, Leucine and Isoleucine DegradationSMP00032map00280
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified14.0 (0.0-28.0) uMChildren (1-13 years old)BothNormal details
BloodDetected and Quantified11.0 +/- 1.7 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified6 +/- 3 uMNot SpecifiedBothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified8.2 +/- 6.8 uMAdult (>18 years old)BothNormal details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
SalivaDetected and Quantified0.679 +/- 0.369 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified0.752 +/- 0.287 uMAdult (>18 years old)Not Specified
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified1.06 +/- 0.436 uMAdult (>18 years old)Not Specified
Normal
    • Sugimoto et al. (...
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified0.345 +/- 0.858 uMAdult (>18 years old)Male
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified0.434 +/- 0.382 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified0.656 +/- 0.399 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
UrineDetected and Quantified0.16 +/- 0.48 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified0.5 (0.2-1.1) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.13 (0.00-0.54) umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified0.07 (0.01-0.45) umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified0.07 (0.01-0.45) umol/mmol creatinineAdult (>18 years old)FemaleNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified10.7 +/- 5.5 uMAdult (>18 years old)Not SpecifiedHeart Transplant details
UrineDetected and Quantified1.00 (0.00-2.00) umol/mmol creatinineAdult (>18 years old)BothMaple syrup urine disease details
UrineDetected and Quantified550.00 (300.00-800.00) umol/mmol creatinineChildren (1-13 years old)BothMaple syrup urine disease (MSUD) details
Associated Disorders and Diseases
Disease References
Maple syrup urine disease
  1. MetaGene [Link]
Associated OMIM IDs
DrugBank IDDB04074
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB012250
KNApSAcK IDC00007623
Chemspider ID48
KEGG Compound IDC00141
BioCyc ID2-KETO-ISOVALERATE
BiGG ID34011
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00019
Metagene LinkHMDB00019
METLIN ID5091
PubChem Compound49
PDB IDKIV
ChEBI ID16530
References
Synthesis ReferencePirrung, 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
  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 ]

Enzymes

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
  1. 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. [6822537 ]
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
  1. 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. [6822537 ]
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
  1. 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. [6822537 ]
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
  1. 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. [6822537 ]
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 dioxidedetails
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 dioxidedetails
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 aciddetails
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 aciddetails
References
  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 ]

Transporters

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
  1. 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. [11101640 ]
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
  1. 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. [9639576 ]
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
  1. 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. [10417314 ]