2.0 2012-05-31 09:55:11 -0600 2015-06-03 15:00:41 -0600 ECMDB00005 M2MDB000001 2-Ketobutyric acid 2-Ketobutyric acid (alpha ketobutyric acid) is involved in the metabolism of many amino acids (glycine, cysteine, methionine, valine, leucine, serine, threonine, isoleucine). It also plays a role in propanoate metabolism and C-5 branched dibasic acid metabolism. More specifically, alpha-ketobutyric acid can be produced through the lysis of cystathionine (via cystathionine gamma lyase) leading to the production of cysteine and alpha-ketobutyric acid. It is also one of the degradation products of threonine. It can be converted to propionyl-CoA (and subsequently methylmalonyl CoA, which can be converted to succinyl CoA, a citric acid cycle intermediate), and thus enter the citric acid cycle. &alpha;-ketobutyrate &alpha;-ketobutyric acid &alpha;-oxobutyrate &alpha;-oxobutyric acid 2-Keto-butyrate 2-Keto-butyric acid 2-Ketobutanoate 2-Ketobutanoic acid 2-Ketobutyrate 2-Ketobutyric acid 2-OBA 2-Oxo-Butanoate 2-Oxo-Butanoic acid 2-Oxo-Butyrate 2-Oxo-Butyric acid 2-Oxo-N-butyrate 2-Oxo-N-butyric acid 2-Oxobutanoate 2-Oxobutanoic acid 2-Oxobutyrate 2-Oxobutyric acid 3-Methylpyruvate 3-Methylpyruvic acid A-Keto-N-Butyrate A-Keto-N-Butyric acid a-Ketobutrate a-Ketobutric acid A-Ketobutyrate A-Ketobutyric acid A-Oxo-N-butyrate A-Oxo-N-butyric acid A-Oxobutyrate A-Oxobutyric acid Alpha-Keto-N-butyrate Alpha-Keto-N-butyric acid Alpha-Ketobutrate Alpha-Ketobutric acid Alpha-Ketobutyrate Alpha-Ketobutyric acid Alpha-Oxo-N-butyrate Alpha-Oxo-N-butyric acid Alpha-Oxobutyrate Alpha-Oxobutyric acid Methyl-Pyruvate Methyl-Pyruvic acid Propionyl-formate Propionyl-formic acid α-keto-N-Butyrate α-keto-N-Butyric acid α-Ketobutrate α-Ketobutric acid α-Ketobutyrate α-Ketobutyric acid α-oxo-N-Butyrate α-oxo-N-Butyric acid α-Oxobutyrate α-Oxobutyric acid C4H6O3 102.0886 102.031694058 (1S,2R,3R,7S,7aR)-3-(hydroxymethyl)-hexahydro-1H-pyrrolizine-1,2,7-triol (1S,2R,3R,7S,7aR)-3-(hydroxymethyl)-hexahydro-1H-pyrrolizine-1,2,7-triol 600-18-0 CCC(=O)C(O)=O InChI=1S/C4H6O3/c1-2-3(5)4(6)7/h2H2,1H3,(H,6,7) TYEYBOSBBBHJIV-UHFFFAOYSA-N Solid Cytosol logp -2.05 ALOGPS logs 0.79 ALOGPS solubility 1.16e+03 g/l ALOGPS melting_point 33oC [Suante, H.; Oxidation Communications 2004, V27(2), P344-348] logp -2.6 ChemAxon pka_strongest_acidic 13.15 ChemAxon pka_strongest_basic 8.73 ChemAxon iupac (1S,2R,3R,7S,7aR)-3-(hydroxymethyl)-hexahydro-1H-pyrrolizine-1,2,7-triol ChemAxon average_mass 102.0886 ChemAxon mono_mass 102.031694058 ChemAxon smiles CCC(=O)C(O)=O ChemAxon formula C4H6O3 ChemAxon inchi InChI=1S/C4H6O3/c1-2-3(5)4(6)7/h2H2,1H3,(H,6,7) ChemAxon inchikey TYEYBOSBBBHJIV-UHFFFAOYSA-N ChemAxon polar_surface_area 84.16 ChemAxon refractivity 44.44 ChemAxon polarizability 18.88 ChemAxon rotatable_bond_count 1 ChemAxon acceptor_count 5 ChemAxon donor_count 4 ChemAxon physiological_charge 1 ChemAxon formal_charge 0 ChemAxon Cysteine and methionine metabolism ec00270 Glycine, serine and threonine metabolism ec00260 Valine, leucine and isoleucine biosynthesis ec00290 C5-Branched dibasic acid metabolism ec00660 Propanoate metabolism Starting from L-threonine, this compound is deaminated through a threonine deaminase resulting in a hydrogen ion, a water molecule and a (2z)-2-aminobut-2-enoate. The latter compound then isomerizes to a 2-iminobutanoate, This compound then reacts spontaneously with hydrogen ion and a water molecule resulting in a ammonium and a 2-Ketobutyric acid. The latter compound interacts with CoA through a pyruvate formate-lyase / 2-ketobutyrate formate-lyase resulting in a formic acid and a propionyl-CoA. Propionyl-CoA can then be processed either into a 2-methylcitric acid or into a propanoyl phosphate. Propionyl-CoA interacts with oxalacetic acid and a water molecule through a 2-methylcitrate synthase resulting in a hydrogen ion, a CoA and a 2-Methylcitric acid.The latter compound is dehydrated through a 2-methylcitrate dehydratase resulting in a water molecule and cis-2-methylaconitate. The latter compound is then dehydrated by a bifunctional aconitate hydratase 2 and 2-methylisocitrate dehydratase resulting in a water molecule and methylisocitric acid. The latter compound is then processed by 2-methylisocitrate lyase resulting in a release of succinic acid and pyruvic acid. Succinic acid can then interact with a propionyl-CoA through a propionyl-CoA:succinate CoA transferase resulting in a propionic acid and a succinyl CoA. Succinyl-CoA is then isomerized through a methylmalonyl-CoA mutase resulting in a methylmalonyl-CoA. This compound is then decarboxylated through a methylmalonyl-CoA decarboxylase resulting in a release of Carbon dioxide and Propionyl-CoA. ropionyl-CoA interacts with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. Propionyl-CoA can react with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. The latter compound is then dephosphorylated through a ADP driven acetate kinase/propionate kinase protein complex resulting in an ATP and Propionic acid. Propionic acid can be processed by a reaction with CoA through a ATP-driven propionyl-CoA synthetase resulting in a pyrophosphate, an AMP and a propionyl-CoA. PW000940 ec00640 Metabolic Metabolic pathways eco01100 isoleucine biosynthesis Isoleucine biosynthesis begins with L-threonine from the threonine biosynthesis pathway. L-threonine interacts with a threonine dehydratase biosynthetic releasing water, a hydrogen ion and (2Z)-2-aminobut-2-enoate. This compound is isomerized into a 2-iminobutanoate which interacts with water and a hydrogen ion spontaneously, resulting in the release of ammonium and 2-ketobutyric acid. This compound reacts with pyruvic acid and hydrogen ion through an acetohydroxybutanoate synthase / acetolactate synthase 2 resulting in carbon dioxide and (S)-2-Aceto-2-hydroxybutanoic acid. The latter compound is reduced by an NADPH driven acetohydroxy acid isomeroreductase releasing NADP and acetohydroxy acid isomeroreductase. The latter compound is dehydrated by a dihydroxy acid dehydratase resulting in 3-methyl-2-oxovaleric acid.This compound reacts in a reversible reaction with L-glutamic acid through a Branched-chain-amino-acid aminotransferase resulting in oxoglutaric acid and L-isoleucine. L-isoleucine can also be transported into the cytoplasm through two different methods: a branched chain amino acid ABC transporter or a branched chain amino acid transporter BrnQ y. PW000818 Metabolic isoleucine biosynthesis I (from threonine) ILEUSYN-PWY threonine degradation I PWY-5437 Specdb::MsMs 1291855 Specdb::MsMs 1291856 Specdb::MsMs 1291857 Specdb::MsMs 1406548 Specdb::MsMs 1406549 Specdb::MsMs 1406550 HMDB00005 58 57 C00109 16763 2-OXOBUTANOATE 2KT Alpha-ketobutyric_acid 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. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 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. 17765195 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. 18331064 Sprague CL, Elfarra AA: Detection of carboxylic acids and inhibition of hippuric acid formation in rats treated with 3-butene-1,2-diol, a major metabolite of 1,3-butadiene. Drug Metab Dispos. 2003 Aug;31(8):986-92. 12867486 Yaegaki K, Sanada K: Biochemical and clinical factors influencing oral malodor in periodontal patients. J Periodontol. 1992 Sep;63(9):783-9. 1474480 Yaegaki K, Sanada K: Effects of a two-phase oil-water mouthwash on halitosis. Clin Prev Dent. 1992 Jan-Feb;14(1):5-9. 1499240 Yang W, Roth KS: Defect in alpha-ketobutyrate metabolism: a new inborn error. Clin Chim Acta. 1985 Jan 30;145(2):173-82. 3918815 Figge, Rainer; Lux, Fabien; Raynaud, Celine; Soucaille, Philippe. Production of a-ketobutyrate by engineered Escherichia coli.PCT Int. Appl. (2006), 31pp. Acetolactate synthase isozyme 3 large subunit P00893 ILVI_ECOLI ilvI http://ecmdb.ca/proteins/P00893.xml Acetolactate synthase isozyme 3 small subunit P00894 ILVH_ECOLI ilvH http://ecmdb.ca/proteins/P00894.xml Cystathionine gamma-synthase P00935 METB_ECOLI metB http://ecmdb.ca/proteins/P00935.xml Threonine dehydratase biosynthetic P04968 THD1_ECOLI ilvA http://ecmdb.ca/proteins/P04968.xml Acetolactate synthase isozyme 1 large subunit P08142 ILVB_ECOLI ilvB http://ecmdb.ca/proteins/P08142.xml Valine--pyruvate aminotransferase P09053 AVTA_ECOLI avtA http://ecmdb.ca/proteins/P09053.xml Formate acetyltransferase 1 P09373 PFLB_ECOLI pflB http://ecmdb.ca/proteins/P09373.xml Pyruvate formate-lyase 1-activating enzyme P0A9N4 PFLA_ECOLI pflA http://ecmdb.ca/proteins/P0A9N4.xml Acetolactate synthase isozyme 1 small subunit P0ADF8 ILVN_ECOLI ilvN http://ecmdb.ca/proteins/P0ADF8.xml Acetolactate synthase isozyme 2 small subunit P0ADG1 ILVM_ECOLI ilvM http://ecmdb.ca/proteins/P0ADG1.xml Threonine dehydratase catabolic P0AGF6 THD2_ECOLI tdcB http://ecmdb.ca/proteins/P0AGF6.xml 3-isopropylmalate dehydrogenase P30125 LEU3_ECOLI leuB http://ecmdb.ca/proteins/P30125.xml Formate acetyltransferase 2 P32674 PFLD_ECOLI pflD http://ecmdb.ca/proteins/P32674.xml Keto-acid formate acetyltransferase P42632 TDCE_ECOLI tdcE http://ecmdb.ca/proteins/P42632.xml Putative formate acetyltransferase 3 P75793 PFLF_ECOLI ybiW http://ecmdb.ca/proteins/P75793.xml Autonomous glycyl radical cofactor P68066 GRCA_ECOLI grcA http://ecmdb.ca/proteins/P68066.xml UPF0076 protein yjgF P0AF93 YJGF_ECOLI yjgF http://ecmdb.ca/proteins/P0AF93.xml 2-Ketobutyric acid + Hydrogen ion + Pyruvic acid > 2-Aceto-2-hydroxy-butyrate + Carbon dioxide R08648 ACETOOHBUTSYN-RXN L-Threonine > 2-Ketobutyric acid + Ammonium 2-Ketobutyric acid + Carbon dioxide + NADH + Hydrogen ion <> D-Erythro-3-Methylmalate + NAD R00994 L-Threonine <> 2-Ketobutyric acid + Ammonia R00996 O-Succinyl-L-homoserine + Water <> 2-Ketobutyric acid + Succinic acid + Ammonia R00999 2-Ketobutyric acid + 2-(a-Hydroxyethyl)thiamine diphosphate <> 2-Aceto-2-hydroxy-butyrate + Thiamine pyrophosphate R04673 2-Ketobutyric acid + Coenzyme A <> Propionyl-CoA + Formic acid R06987 Pyruvic acid + 2-Ketobutyric acid <> 2-Aceto-2-hydroxy-butyrate + Carbon dioxide R08648 2-Ketobutyric acid + Coenzyme A > Propionyl-CoA + Formic acid KETOBUTFORMLY-RXN Hydrogen ion + 2-Ketobutyric acid + Succinic acid + Ammonia O-Succinyl-L-homoserine + Water R00999 METBALT-RXN an aminated amine donor + 2-Ketobutyric acid + Hydrogen ion 2-aminobutyrate + a deaminated amine donor RXN0-5200 L-Threonine > Hydrogen ion + 2-Ketobutyric acid + Ammonia R00996 THREDEHYD-RXN L-Threonine > 2-Ketobutyric acid + Ammonia R00996 THREDEHYD-RXN Iminobutyrate + Water > 2-Ketobutyric acid + Ammonia Propionyl-CoA + Formic acid > CoA + 2-Ketobutyric acid L-Threonine + 2-Aminobut-2-enoate + 2-Iminobutanoate + Water <> 2-Ketobutyric acid + Ammonia R00996 2-Ketobutyric acid + Coenzyme A > Formic acid + Propionyl-CoA + Propionyl-CoA PW_R003493 2 2-Ketobutyric acid + Hydrogen ion + Pyruvic acid >2 2-Aceto-2-hydroxy-butyrate + Carbon dioxide 2 2-Ketobutyric acid + Hydrogen ion + Pyruvic acid >2 2-Aceto-2-hydroxy-butyrate + Carbon dioxide