ECMDB: Ketoleucine (ECMDB00695) (M2MDB000174)

Identification Taxonomy Physical Properties Biological Properties Spectra Concentrations Links References Enzymes (3)XML

Proteins (1211)

Record Information

Version

2.0

Creation Date

2012-05-31 13:00:31 -0600

Update Date

2015-09-13 12:56:08 -0600

Secondary Accession Numbers

ECMDB00695

Identification

Name:

Ketoleucine

Description

Ketoleucine belongs to the class of Branched Fatty Acids. These are fatty acids containing a branched chain. (inferred from compound structure) Ketoleucine is also known by names such as 4-methyl-2-oxopentanoic acid and 2-Oxoisocaproic acid. (PubChem) In E. coli, the enzyme branched-chain amino acid aminotransferase (EC:2.6.1.42) catalyses the reversible conversion between ketoleucine and L-leucine. (KEGG)

Structure

MOL SDF PDB SMILES InChI

Synonyms:

α-ketoisocaproate
α-ketoisocaproic acid
α-oxoisocaproate
α-oxoisocaproic acid
2-Keto-4-methyl-pentanoate
2-Keto-4-methyl-pentanoic acid
2-Keto-4-Methylvalerate
2-Keto-4-Methylvaleric acid
2-Ketoisocaproate
2-Ketoisocaproic acid
2-Oxo-4-methylpentanoate
2-Oxo-4-methylpentanoic acid
2-Oxo-4-methylvalerate
2-Oxo-4-methylvaleric acid
2-Oxoisocaproate
2-Oxoisocaproic acid
2-Oxoleucine
2KICA
4-Methyl-2-oxo-Valerate
4-Methyl-2-oxo-Valeric acid
4-Methyl-2-oxopentanoate
4-Methyl-2-oxopentanoic acid
a-keto-Isocaproate
a-keto-Isocaproic acid
A-Ketoisocaproate
A-Ketoisocaproic acid
A-Ketoisocapronate
A-Ketoisocapronic acid
A-Oxoisocaproate
A-Oxoisocaproic acid
Alpha-keto-isocaproate
Alpha-keto-isocaproic acid
alpha-Ketoisocaproate
alpha-Ketoisocaproic acid
Alpha-Ketoisocapronate
Alpha-Ketoisocapronic acid
alpha-Oxoisocaproate
alpha-Oxoisocaproic acid
Ketoisocaproate
Ketoisocaproic acid
Methyloxovalerate
Methyloxovaleric acid
Oxoisocaproate
Oxoisocaproic acid
α-keto-Isocaproate
α-keto-Isocaproic acid
α-Ketoisocaproate
α-Ketoisocaproic acid
α-Ketoisocapronate
α-Ketoisocapronic acid
α-Oxoisocaproate
α-Oxoisocaproic acid

Chemical Formula:

C₆H₁₀O₃

Weight:

Average: 130.1418
Monoisotopic: 130.062994186

InChI Key:

BKAJNAXTPSGJCU-UHFFFAOYSA-N

InChI:

InChI=1S/C6H10O3/c1-4(2)3-5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9)

CAS number:

816-66-0

IUPAC Name:

4-methyl-2-oxopentanoic acid

Traditional IUPAC Name:

ketoisocaproate

SMILES:

CC(C)CC(=O)C(O)=O

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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Keto acids and derivatives

Sub Class

Short-chain keto acids and derivatives

Direct Parent

Short-chain keto acids and derivatives

Alternative Parents

Substituents

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 Framework

Aliphatic acyclic compounds

External Descriptors

2-oxo monocarboxylic acid (CHEBI:48430 )

Physical Properties

State:

Liquid

Charge:

-1

Melting point:

8-10 °C

Experimental Properties:

Property	Value	Source

Predicted Properties

Property	Value	Source
Water Solubility	6.76 g/L	ALOGPS
logP	0.82	ALOGPS
logP	1.5	ChemAxon
logS	-1.3	ALOGPS
pKa (Strongest Acidic)	3.53	ChemAxon
pKa (Strongest Basic)	-9.7	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	54.37 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	31.77 m³·mol⁻¹	ChemAxon
Polarizability	13 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Biological Properties

Cellular Locations:

Cytoplasm

Reactions:

Ketoleucine + L-Glutamate > alpha-Ketoglutarate + L-Leucine
2-Isopropyl-3-oxosuccinate + Hydrogen ion > Ketoleucine + Carbon dioxide
L-Leucine + alpha-Ketoglutarate <> 4-Methyl-2-oxopentanoate + L-Glutamate + Ketoleucine
L-Leucine + Oxoglutaric acid <> Ketoleucine + L-Glutamate
L-Leucine + Oxoglutaric acid > Ketoleucine + L-Glutamate
3-Isopropylmalate + NAD > Ketoleucine + Carbon dioxide + NADH
3-Isopropylmalate + NAD + 2-Isopropyl-3-oxosuccinate <> Ketoleucine + Carbon dioxide + NADH + Hydrogen ion
Ketoleucine + L-Glutamic acid + L-Glutamate > Oxoglutaric acid + L-Leucine

SMPDB Pathways:

Leucine Biosynthesis	PW000811
Pantothenate and CoA biosynthesis	PW000828
Secondary Metabolite: Leucine biosynthesis	PW000980
Secondary Metabolites: Valine and I-leucine biosynthesis from pyruvate	PW000978

KEGG Pathways:

C5-Branched dibasic acid metabolism ec00660
Glucosinolate biosynthesis ec00966
Metabolic pathways eco01100
Pantothenate and CoA biosynthesis ec00770
Valine, leucine and isoleucine biosynthesis ec00290
Valine, leucine and isoleucine degradation ec00280

EcoCyc Pathways:

isoleucine biosynthesis I (from threonine) LEUSYN-PWY

Concentrations

Not Available

Spectra

Spectra:

Spectrum Type	Description	Splash Key
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-000i-9400000000-49d055f04bfe1877ac5b	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-029j-8930000000-c6c54bf6ee2995a2195b	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-0002-1910000000-0ba38257e25873312809	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-0a5c-4930000000-61247369a805fa2a77a7	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)	splash10-000i-9510000000-8bfc5a54e29f65edf361	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)	splash10-00lj-9620000000-aa8409ceb2359d903f38	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-9400000000-49d055f04bfe1877ac5b	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-029j-8930000000-c6c54bf6ee2995a2195b	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-1910000000-0ba38257e25873312809	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0a5c-4930000000-61247369a805fa2a77a7	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-000i-9510000000-8bfc5a54e29f65edf361	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-00lj-9620000000-aa8409ceb2359d903f38	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00ks-7930000000-4e9cfd715fa884d30e7f	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-9500000000-709ebcb57f006703c269	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0006-9000000000-e410bce23706f826f8dd	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0006-9400000000-c4f06cea1e27a2b24660	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	View in JSpectraViewer
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-0006-9000000000-bed7ac074a60210971e3	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-014i-9200000000-2fa08d2b4df406cf63ea	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-014j-9000000000-045be8e8dca3f93d45ba	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-004i-0900000000-237fa8ad6bfb929be31e	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-004r-9700000000-8d38d24fce78b1ff13e6	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-0a59-9000000000-759cfc0817917283d1a5	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-0a4l-9000000000-2a068ada71fbe0a5a988	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-0a4l-9000000000-58e61e31f3c96d84d799	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-004i-0900000000-237fa8ad6bfb929be31e	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-004r-9700000000-8d38d24fce78b1ff13e6	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a59-9000000000-759cfc0817917283d1a5	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4l-9000000000-2a068ada71fbe0a5a988	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4l-9000000000-58e61e31f3c96d84d799	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , negative	splash10-004i-0900000000-556a0d1cf568609752d1	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , negative	splash10-004r-5900000000-20f6923c8ed45e9fa088	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-004i-0900000000-b66d521478c92e2d77d0	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0900000000-9c3a698d9f28af574ef6	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-03di-9000000000-47ced70de4860e900283	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-03xr-7900000000-0461a5a56e36a03fe522	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-08gr-7900000000-31021fda89eb6535185f	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0btm-9200000000-3bf5df4b557ef87267f4	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-37839bf70647d24b94a4	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-4900000000-796467909d1d4c087a07	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01ri-9400000000-0abcd021721f32c10e42	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-015l-9000000000-5c33a47dfeb09a182983	View in MoNA
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	View in JSpectraViewer

References

References:

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. Pubmed: 16705065
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. Pubmed: 1858984
Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. Pubmed: 21097882
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. Pubmed: 16805814
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. Pubmed: 7462428
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. Pubmed: 10472531
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. Pubmed: 14636955
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. Pubmed: 19212411
van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. Pubmed: 17765195
Vijayendran, C., Barsch, A., Friehs, K., Niehaus, K., Becker, A., Flaschel, E. (2008). "Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling." Genome Biol 9:R72. Pubmed: 18402659
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. Pubmed: 15314235
Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. Pubmed: 18331064
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. Pubmed: 15930465
Yurtsever D. (2007). Fatty acid methyl ester profiling of Enterococcus and Esherichia coli for microbial source tracking. M.sc. Thesis. Villanova University: U.S.A

Synthesis Reference:

Not Available

Material Safety Data Sheet (MSDS)

Download (PDF)

Links

External Links:

Resource	Link
CHEBI ID	48430
HMDB ID	HMDB00695
Pubchem Compound ID	70
Kegg ID	C00233
ChemSpider ID	69
Wikipedia ID	Not Available
BioCyc ID	2K-4CH3-PENTANOATE
EcoCyc ID	2K-4CH3-PENTANOATE
Ligand Expo	COI

Enzymes

Protein Details

1. Aromatic-amino-acid aminotransferase

General function:: Involved in transferase activity
Specific function:: An aromatic amino acid + 2-oxoglutarate = an aromatic oxo acid + L-glutamate
Gene Name:: tyrB
Uniprot ID:: P04693
Molecular weight:: 43537

Reactions

An aromatic amino acid + 2-oxoglutarate = an aromatic oxo acid + L-glutamate.

Protein Details

2. 3-isopropylmalate dehydrogenase

General function:: Involved in magnesium ion binding
Specific function:: Catalyzes the oxidation of 3-carboxy-2-hydroxy-4- methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2- oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate
Gene Name:: leuB
Uniprot ID:: P30125
Molecular weight:: 39517

Reactions

(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl-2-oxopentanoate + CO(2) + NADH.

Protein Details

3. Branched-chain-amino-acid aminotransferase

General function:: Involved in catalytic activity
Specific function:: Acts on leucine, isoleucine and valine
Gene Name:: ilvE
Uniprot ID:: P0AB80
Molecular weight:: 34093

Reactions

L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate.
L-isoleucine + 2-oxoglutarate = (S)-3-methyl-2-oxopentanoate + L-glutamate.
L-valine + 2-oxoglutarate = 3-methyl-2-oxobutanoate + L-glutamate.

Ketoleucine (ECMDB00695) (M2MDB000174)

Structure for #<Compound:0xa17a1920>

Enzymes

Reactions

Reactions

Reactions