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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-08-17 21:41:51 UTC
HMDB IDHMDB00695
Secondary Accession Numbers
  • HMDB00762
Metabolite Identification
Common NameKetoleucine
DescriptionKetoleucine is a metabolite that accumulates in Maple Syrup Urine Disease (MSUD) and shown to compromise brain energy metabolism by blocking the respiratory chain; this is of relevance to the understanding of the pathophysiology of the neurological dysfunction of MSUD patients. (PMID 14636955 ).
Structure
Thumb
Synonyms
ValueSource
2-OxoisocaproateKegg
2-Oxoisocaproic acidGenerator
2-keto-4-MethylvalerateHMDB
2-keto-4-Methylvaleric acidHMDB
2-KetoisocaproateHMDB
2-Ketoisocaproic acidHMDB
2-oxo-4-MethylpentanoateHMDB
2-oxo-4-Methylpentanoic acidHMDB
2-oxo-4-MethylvalerateHMDB
2-oxo-4-Methylvaleric acidHMDB
2-OxoleucineHMDB
4-Methyl-2-oxo-valerateHMDB
4-Methyl-2-oxo-valeric acidHMDB
4-Methyl-2-oxopentanoateHMDB
4-Methyl-2-oxopentanoic acidHMDB
a-KetoisocaproateHMDB
a-Ketoisocaproic acidHMDB
a-KetoisocapronateHMDB
a-Ketoisocapronic acidHMDB
a-OxoisocaproateHMDB
a-Oxoisocaproic acidHMDB
alpha-keto-IsocaproateHMDB
alpha-keto-Isocaproic acidHMDB
alpha-KetoisocaproateHMDB
alpha-Ketoisocaproic acidHMDB
alpha-KetoisocapronateHMDB
alpha-Ketoisocapronic acidHMDB
alpha-OxoisocaproateHMDB
alpha-Oxoisocaproic acidHMDB
KetoisocaproateHMDB
Ketoisocaproic acidHMDB
MethyloxovalerateHMDB
Methyloxovaleric acidHMDB
OxoisocaproateHMDB
Oxoisocaproic acidHMDB
Chemical FormulaC6H10O3
Average Molecular Weight130.1418
Monoisotopic Molecular Weight130.062994186
IUPAC Name4-methyl-2-oxopentanoic acid
Traditional Nameketoisocaproate
CAS Registry Number816-66-0
SMILES
CC(C)CC(=O)C(O)=O
InChI Identifier
InChI=1S/C6H10O3/c1-4(2)3-5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9)
InChI KeyInChIKey=BKAJNAXTPSGJCU-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound 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
Substituents
  • Methyl-branched fatty acid
  • Short-chain keto acid
  • Branched fatty acid
  • Fatty acyl
  • Alpha-keto acid
  • Alpha-hydroxy ketone
  • Ketone
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Component of Pantothenate and CoA biosynthesis
  • Component of Valine, leucine and isoleucine biosynthesis
  • 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
StateLiquid
Experimental Properties
PropertyValueReference
Melting Point8 - 10 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility32 mg/mLNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility6.76 mg/mLALOGPS
logP0.82ALOGPS
logP1.5ChemAxon
logS-1.3ALOGPS
pKa (Strongest Acidic)3.53ChemAxon
pKa (Strongest Basic)-9.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity31.77 m3·mol-1ChemAxon
Polarizability13 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-000i-9400000000-49d055f04bfe1877ac5bView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-029j-8930000000-c6c54bf6ee2995a2195bView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-0002-1910000000-0ba38257e25873312809View in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0a5c-4930000000-61247369a805fa2a77a7View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-000i-9510000000-8bfc5a54e29f65edf361View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-00lj-9620000000-aa8409ceb2359d903f38View in MoNA
GC-MSGC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0006-9000000000-bed7ac074a60210971e3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-014i-9200000000-2fa08d2b4df406cf63eaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014j-9000000000-045be8e8dca3f93d45baView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-004i-0900000000-237fa8ad6bfb929be31eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-004r-9700000000-8d38d24fce78b1ff13e6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0a59-9000000000-759cfc0817917283d1a5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0a4l-9000000000-2a068ada71fbe0a5a988View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0a4l-9000000000-58e61e31f3c96d84d799View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-08gr-7900000000-31021fda89eb6535185fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0btm-9200000000-3bf5df4b557ef87267f4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-37839bf70647d24b94a4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-4900000000-796467909d1d4c087a07View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ri-9400000000-0abcd021721f32c10e42View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-015l-9000000000-5c33a47dfeb09a182983View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Muscle
  • Neuron
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
2-Methyl-3-Hydroxybutryl CoA Dehydrogenase DeficiencySMP00137Not Available
3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencySMP00138Not Available
3-hydroxyisobutyric acid dehydrogenase deficiencySMP00521Not Available
3-hydroxyisobutyric aciduriaSMP00522Not Available
3-Methylcrotonyl Coa Carboxylase Deficiency Type ISMP00237Not Available
3-Methylglutaconic Aciduria Type ISMP00139Not Available
3-Methylglutaconic Aciduria Type IIISMP00140Not Available
3-Methylglutaconic Aciduria Type IVSMP00141Not Available
Beta-Ketothiolase DeficiencySMP00173Not Available
Isobutyryl-coa dehydrogenase deficiencySMP00523Not Available
Isovaleric acidemiaSMP00524Not Available
Isovaleric AciduriaSMP00238Not Available
Maple Syrup Urine DiseaseSMP00199Not Available
Methylmalonate Semialdehyde Dehydrogenase DeficiencySMP00384Not Available
Methylmalonic AciduriaSMP00200Not Available
Propionic AcidemiaSMP00236Not Available
Valine, Leucine and Isoleucine DegradationSMP00032map00280
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified28.0 (0.0-58.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified33.5 +/- 8.2 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified5.0 +/- 4.4 uMAdult (>18 years old)BothNormal details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
SalivaDetected and Quantified0.944 +/- 0.442 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified1.24 +/- 0.728 uMAdult (>18 years old)Female
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
UrineDetected and Quantified0.48-0.86 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified1.623 +/- 1.21 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified0.48-0.72 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified0.13 (0.02-0.45) umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified0.13 (0.03-0.34) umol/mmol creatinineAdult (>18 years old)FemaleNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected and Quantified1.407 +/- 0.928 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB03229
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB012607
KNApSAcK IDC00019677
Chemspider ID69
KEGG Compound IDC00233
BioCyc ID2K-4CH3-PENTANOATE
BiGG ID34334
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00695
Metagene LinkHMDB00695
METLIN ID5663
PubChem Compound70
PDB IDCOI
ChEBI ID48430
References
Synthesis ReferenceTabuchi, Takeshi; Abe, Matazo. Fermentative preparation of a-ketoisocaproic acid. Jpn. Tokkyo Koho (1970), 3 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Martin PM, Gopal E, Ananth S, Zhuang L, Itagaki S, Prasad BM, Smith SB, Prasad PD, Ganapathy V: Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain. J Neurochem. 2006 Jul;98(1):279-88. [16805814 ]
  2. 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. [19212411 ]
  3. 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. [15930465 ]
  4. Chow LS, Albright RC, Bigelow ML, Toffolo G, Cobelli C, Nair KS: Mechanism of insulin's anabolic effect on muscle: measurements of muscle protein synthesis and breakdown using aminoacyl-tRNA and other surrogate measures. Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E729-36. Epub 2006 May 16. [16705065 ]
  5. Wang Y, Holmes E, Nicholson JK, Cloarec O, Chollet J, Tanner M, Singer BH, Utzinger J: Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12676-81. Epub 2004 Aug 16. [15314235 ]
  6. Mitch WE, Walser M, Sapir DG: Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man. J Clin Invest. 1981 Feb;67(2):553-62. [7462428 ]
  7. Sgaravatti AM, Rosa RB, Schuck PF, Ribeiro CA, Wannmacher CM, Wyse AT, Dutra-Filho CS, Wajner M: Inhibition of brain energy metabolism by the alpha-keto acids accumulating in maple syrup urine disease. Biochim Biophys Acta. 2003 Nov 20;1639(3):232-8. [14636955 ]
  8. Schadewaldt P, Hammen HW, Ott AC, Wendel U: Renal clearance of branched-chain L-amino and 2-oxo acids in maple syrup urine disease. J Inherit Metab Dis. 1999 Aug;22(6):706-22. [10472531 ]
  9. Hachey DL, Patterson BW, Reeds PJ, Elsas LJ: Isotopic determination of organic keto acid pentafluorobenzyl esters in biological fluids by negative chemical ionization gas chromatography/mass spectrometry. Anal Chem. 1991 May 1;63(9):919-23. [1858984 ]

Enzymes

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
Ketoleucine + Thiamine pyrophosphate → 3-Methyl-1-hydroxybutyl-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
Ketoleucine + Thiamine pyrophosphate → 3-Methyl-1-hydroxybutyl-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-Leucine + Oxoglutaric acid → Ketoleucine + 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-Leucine + Oxoglutaric acid → Ketoleucine + L-Glutamic aciddetails