2.02012-05-31 09:55:11 -06002015-06-03 15:00:41 -0600ECMDB00005M2MDB0000012-Ketobutyric acid2-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.α-ketobutyrateα-ketobutyric acidα-oxobutyrateα-oxobutyric acid2-Keto-butyrate2-Keto-butyric acid2-Ketobutanoate2-Ketobutanoic acid2-Ketobutyrate2-Ketobutyric acid2-OBA2-Oxo-Butanoate2-Oxo-Butanoic acid2-Oxo-Butyrate2-Oxo-Butyric acid2-Oxo-N-butyrate2-Oxo-N-butyric acid2-Oxobutanoate2-Oxobutanoic acid2-Oxobutyrate2-Oxobutyric acid3-Methylpyruvate3-Methylpyruvic acidA-Keto-N-ButyrateA-Keto-N-Butyric acida-Ketobutratea-Ketobutric acidA-KetobutyrateA-Ketobutyric acidA-Oxo-N-butyrateA-Oxo-N-butyric acidA-OxobutyrateA-Oxobutyric acidAlpha-Keto-N-butyrateAlpha-Keto-N-butyric acidAlpha-KetobutrateAlpha-Ketobutric acidAlpha-KetobutyrateAlpha-Ketobutyric acidAlpha-Oxo-N-butyrateAlpha-Oxo-N-butyric acidAlpha-OxobutyrateAlpha-Oxobutyric acidMethyl-PyruvateMethyl-Pyruvic acidPropionyl-formatePropionyl-formic acidα-keto-N-Butyrateα-keto-N-Butyric acidα-Ketobutrateα-Ketobutric acidα-Ketobutyrateα-Ketobutyric acidα-oxo-N-Butyrateα-oxo-N-Butyric acidα-Oxobutyrateα-Oxobutyric acidC4H6O3102.0886102.031694058(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-triol600-18-0CCC(=O)C(O)=OInChI=1S/C4H6O3/c1-2-3(5)4(6)7/h2H2,1H3,(H,6,7)TYEYBOSBBBHJIV-UHFFFAOYSA-NSolidCytosollogp-2.05logs0.79solubility1.16e+03 g/lmelting_point33oC [Suante, H.; Oxidation Communications 2004, V27(2), P344-348]logp-2.6pka_strongest_acidic13.15pka_strongest_basic8.73iupac(1S,2R,3R,7S,7aR)-3-(hydroxymethyl)-hexahydro-1H-pyrrolizine-1,2,7-triolaverage_mass102.0886mono_mass102.031694058smilesCCC(=O)C(O)=OformulaC4H6O3inchiInChI=1S/C4H6O3/c1-2-3(5)4(6)7/h2H2,1H3,(H,6,7)inchikeyTYEYBOSBBBHJIV-UHFFFAOYSA-Npolar_surface_area84.16refractivity44.44polarizability18.88rotatable_bond_count1acceptor_count5donor_count4physiological_charge1formal_charge0Cysteine and methionine metabolismec00270Glycine, serine and threonine metabolismec00260Valine, leucine and isoleucine biosynthesisec00290C5-Branched dibasic acid metabolismec00660Propanoate 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.PW000940ec00640MetabolicMetabolic pathwayseco01100isoleucine biosynthesisIsoleucine 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.
PW000818Metabolicisoleucine biosynthesis I (from threonine)ILEUSYN-PWYthreonine degradation IPWY-5437Specdb::MsMs1406548Specdb::MsMs1406549Specdb::MsMs1406550Specdb::MsMs1291855Specdb::MsMs1291856Specdb::MsMs1291857HMDB000055857C00109167632-OXOBUTANOATE2KTAlpha-ketobutyric_acidKeseler, 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-D590.21097882Kanehisa, 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-D114.22080510van 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 370:17-25.17765195Winder, 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 80:2939-2948.18331064Sprague 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):986-92.12867486Yaegaki K, Sanada K: Biochemical and clinical factors influencing oral malodor in periodontal patients. J Periodontol. 1992 Sep;63(9):783-9.1474480Yaegaki K, Sanada K: Effects of a two-phase oil-water mouthwash on halitosis. Clin Prev Dent. 1992 Jan-Feb;14(1):5-9.1499240Yang W, Roth KS: Defect in alpha-ketobutyrate metabolism: a new inborn error. Clin Chim Acta. 1985 Jan 30;145(2):173-82.3918815Figge, 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 subunitP00893ILVI_ECOLIilvIhttp://ecmdb.ca/proteins/P00893.xmlAcetolactate synthase isozyme 3 small subunitP00894ILVH_ECOLIilvHhttp://ecmdb.ca/proteins/P00894.xmlCystathionine gamma-synthaseP00935METB_ECOLImetBhttp://ecmdb.ca/proteins/P00935.xmlThreonine dehydratase biosyntheticP04968THD1_ECOLIilvAhttp://ecmdb.ca/proteins/P04968.xmlAcetolactate synthase isozyme 1 large subunitP08142ILVB_ECOLIilvBhttp://ecmdb.ca/proteins/P08142.xmlValine--pyruvate aminotransferaseP09053AVTA_ECOLIavtAhttp://ecmdb.ca/proteins/P09053.xmlFormate acetyltransferase 1P09373PFLB_ECOLIpflBhttp://ecmdb.ca/proteins/P09373.xmlPyruvate formate-lyase 1-activating enzymeP0A9N4PFLA_ECOLIpflAhttp://ecmdb.ca/proteins/P0A9N4.xmlAcetolactate synthase isozyme 1 small subunitP0ADF8ILVN_ECOLIilvNhttp://ecmdb.ca/proteins/P0ADF8.xmlAcetolactate synthase isozyme 2 small subunitP0ADG1ILVM_ECOLIilvMhttp://ecmdb.ca/proteins/P0ADG1.xmlThreonine dehydratase catabolicP0AGF6THD2_ECOLItdcBhttp://ecmdb.ca/proteins/P0AGF6.xml3-isopropylmalate dehydrogenaseP30125LEU3_ECOLIleuBhttp://ecmdb.ca/proteins/P30125.xmlFormate acetyltransferase 2P32674PFLD_ECOLIpflDhttp://ecmdb.ca/proteins/P32674.xmlKeto-acid formate acetyltransferaseP42632TDCE_ECOLItdcEhttp://ecmdb.ca/proteins/P42632.xmlPutative formate acetyltransferase 3P75793PFLF_ECOLIybiWhttp://ecmdb.ca/proteins/P75793.xmlAutonomous glycyl radical cofactorP68066GRCA_ECOLIgrcAhttp://ecmdb.ca/proteins/P68066.xmlUPF0076 protein yjgFP0AF93YJGF_ECOLIyjgFhttp://ecmdb.ca/proteins/P0AF93.xml2-Ketobutyric acid + Hydrogen ion + Pyruvic acid > 2-Aceto-2-hydroxy-butyrate + Carbon dioxideR08648ACETOOHBUTSYN-RXNL-Threonine > 2-Ketobutyric acid + Ammonium2-Ketobutyric acid + Carbon dioxide + NADH + Hydrogen ion <> D-Erythro-3-Methylmalate + NADR00994L-Threonine <> 2-Ketobutyric acid + AmmoniaR00996O-Succinyl-L-homoserine + Water <> 2-Ketobutyric acid + Succinic acid + AmmoniaR009992-Ketobutyric acid + 2-(a-Hydroxyethyl)thiamine diphosphate <> 2-Aceto-2-hydroxy-butyrate + Thiamine pyrophosphateR046732-Ketobutyric acid + Coenzyme A <> Propionyl-CoA + Formic acidR06987Pyruvic acid + 2-Ketobutyric acid <> 2-Aceto-2-hydroxy-butyrate + Carbon dioxideR086482-Ketobutyric acid + Coenzyme A > Propionyl-CoA + Formic acidKETOBUTFORMLY-RXNHydrogen ion + 2-Ketobutyric acid + Succinic acid + Ammonia O-Succinyl-L-homoserine + WaterR00999METBALT-RXNan aminated amine donor + 2-Ketobutyric acid + Hydrogen ion 2-aminobutyrate + a deaminated amine donorRXN0-5200L-Threonine > Hydrogen ion + 2-Ketobutyric acid + AmmoniaR00996THREDEHYD-RXNL-Threonine > 2-Ketobutyric acid + AmmoniaR00996THREDEHYD-RXNIminobutyrate + Water > 2-Ketobutyric acid + AmmoniaPropionyl-CoA + Formic acid > CoA + 2-Ketobutyric acidL-Threonine + 2-Aminobut-2-enoate + 2-Iminobutanoate + Water <> 2-Ketobutyric acid + AmmoniaR00996 2-Ketobutyric acid + Coenzyme A > Formic acid + Propionyl-CoA + Propionyl-CoAPW_R0034932 2-Ketobutyric acid + Hydrogen ion + Pyruvic acid >2 2-Aceto-2-hydroxy-butyrate + Carbon dioxide2 2-Ketobutyric acid + Hydrogen ion + Pyruvic acid >2 2-Aceto-2-hydroxy-butyrate + Carbon dioxide