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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-29 21:47:50 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)
  • 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
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
UrineDetected and Quantified1.00 (0.00-2.00) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified10.7 +/- 5.5 uMAdult (>18 years old)Not SpecifiedHeart Transplant 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
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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 10417314