2.02012-05-31 13:48:58 -06002015-09-17 15:41:10 -0600ECMDB01275M2MDB000321Propionyl-CoAPropionyl-CoA is an intermediate in the metabolism of propanoate. Propionyl-CoA is a substrate for acetyl-CoA synthetase, propionyl-CoA synthetase and 2-methylcitrate synthase. It is also involved in beta-alanine metabolism, Valine, leucine abd isoleucine degradation and C5-branched dibasic acid metabolism pathways.2-methylacetyl-CoA2-methylacetyl-Coenzyme Aa-Methylacetyl-CoAa-Methylacetyl-coenzyme AAlpha-methylacetyl-CoAAlpha-methylacetyl-Coenzyme AN-Propionyl-CoAPropanoyl-CoAPropanoyl-Coenzyme APropionyl-CoAPropionyl-coenzyme Aα-Methylacetyl-CoAα-Methylacetyl-coenzyme AC24H40N7O17P3S823.597823.141423115{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-2-({[hydroxy({hydroxy[(3R)-3-hydroxy-2,2-dimethyl-3-[(2-{[2-(propanoylsulfanyl)ethyl]carbamoyl}ethyl)carbamoyl]propoxy]phosphoryl}oxy)phosphoryl]oxy}methyl)oxolan-3-yl]oxy}phosphonic acidpropionyl-coa317-66-8CCC(=O)SCCNC(=O)CCNC(=O)C(O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP(O)(O)=O)N1C=NC2=C1N=CN=C2NInChI=1S/C24H40N7O17P3S/c1-4-15(33)52-8-7-26-14(32)5-6-27-22(36)19(35)24(2,3)10-45-51(42,43)48-50(40,41)44-9-13-18(47-49(37,38)39)17(34)23(46-13)31-12-30-16-20(25)28-11-29-21(16)31/h11-13,17-19,23,34-35H,4-10H2,1-3H3,(H,26,32)(H,27,36)(H,40,41)(H,42,43)(H2,25,28,29)(H2,37,38,39)/t13-,17-,18-,19?,23-/m1/s1QAQREVBBADEHPA-UXYNFSPESA-NSolidCytosollogp-0.31logs-2.29solubility4.27e+00 g/llogp-5.2pka_strongest_acidic0.82pka_strongest_basic4.01iupac{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-2-({[hydroxy({hydroxy[(3R)-3-hydroxy-2,2-dimethyl-3-[(2-{[2-(propanoylsulfanyl)ethyl]carbamoyl}ethyl)carbamoyl]propoxy]phosphoryl}oxy)phosphoryl]oxy}methyl)oxolan-3-yl]oxy}phosphonic acidaverage_mass823.597mono_mass823.141423115smilesCCC(=O)SCCNC(=O)CCNC(=O)C(O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP(O)(O)=O)N1C=NC2=C1N=CN=C2NformulaC24H40N7O17P3SinchiInChI=1S/C24H40N7O17P3S/c1-4-15(33)52-8-7-26-14(32)5-6-27-22(36)19(35)24(2,3)10-45-51(42,43)48-50(40,41)44-9-13-18(47-49(37,38)39)17(34)23(46-13)31-12-30-16-20(25)28-11-29-21(16)31/h11-13,17-19,23,34-35H,4-10H2,1-3H3,(H,26,32)(H,27,36)(H,40,41)(H,42,43)(H2,25,28,29)(H2,37,38,39)/t13-,17-,18-,19?,23-/m1/s1inchikeyQAQREVBBADEHPA-UXYNFSPESA-Npolar_surface_area363.63refractivity176.83polarizability74.37rotatable_bond_count21acceptor_count17donor_count9physiological_charge-4formal_charge0Reductive carboxylate cycle (CO2 fixation)ec00720C5-Branched dibasic acid metabolismec00660Glyoxylate and dicarboxylate metabolismec00630Glycerolipid metabolismec00561beta-Alanine metabolismThe Beta-Alanine Metabolism starts with a product of Aspartate metabolism. Aspartate is decarboxylated by aspartate 1-decarboxylase, releasing carbon dioxide and Beta-alanine. Beta alanine is then metabolized through a pantothenate synthetase resulting in Pantothenic acid undergoes phosphorylation through a ATP driven pantothenate kinase, resulting in D-4-phosphopantothenate.
Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganismscan synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets.PW000896ec00410MetabolicPropanoate 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.PW000940ec00640MetabolicValine, leucine and isoleucine degradationec00280Microbial metabolism in diverse environmentsec01120Metabolic pathwayseco01100Conversion of Succinate to PropanoateBased on the biochemical functions of a set of enzymes encoded within an operon, the existence of this pathway, resulting in net decarboxylation of succinate to propionate, has been proposed. However, no metabolic role for this pathway was shown. (EcoCyc)PW002058Metabolicpropanoyl CoA degradationThe degradation of propanoyl-CoA starts with propanoyl-CoA undergoing a decarboxylase reaction by reacting with hydrogen carbonate and ATP resulting in the release of a phosphate, an ADP, a hydrogen ion and an S-methylmalonyl-CoA. This compound in turn reacts through an epimerase reaction resulting in the release of a R-methylmalonyl-CoA. This compound in turn can undergo a reversible reaction through a methylmalonyl-CoA mutase resulting in the release of a succinyl-CoA. This compound can be converted back to R-methylmalonyl-CoA through a methylmalonyl-CoA mutase.
Methylmalonyl-CoA can then be converted into propanoyl-CoA through a methylmalonyl CoA decarboxylase . This compound in turn reacts with a succinate through a propionyl-CoA succinate CoA transferase resulting in the release of a propanoate and a succinyl-CoA.PW002057Metabolicthreonine degradation IPWY-54372-methylcitrate cycle IPWY0-42conversion of succinate to propionatePWY0-43methylmalonyl pathwayPROPIONMET-PWYSpecdb::CMs791411Specdb::CMs791412Specdb::CMs791413Specdb::CMs791414Specdb::CMs791415Specdb::CMs791416Specdb::CMs791417Specdb::CMs791418Specdb::NmrOneD87692Specdb::NmrOneD87693Specdb::NmrOneD87694Specdb::NmrOneD87695Specdb::NmrOneD87696Specdb::NmrOneD87697Specdb::NmrOneD87698Specdb::NmrOneD87699Specdb::NmrOneD87700Specdb::NmrOneD87701Specdb::NmrOneD87702Specdb::NmrOneD87703Specdb::NmrOneD87704Specdb::NmrOneD87705Specdb::NmrOneD87706Specdb::NmrOneD87707Specdb::NmrOneD87708Specdb::NmrOneD87709Specdb::NmrOneD87710Specdb::NmrOneD87711Specdb::MsMs22970Specdb::MsMs22971Specdb::MsMs22972Specdb::MsMs29768Specdb::MsMs29769Specdb::MsMs29770Specdb::MsMs2299857Specdb::MsMs2299858Specdb::MsMs2299859Specdb::MsMs2638648Specdb::MsMs2638649Specdb::MsMs2638650HMDB01275439164388310C0010015539PROPIONYL-COAPropionyl-CoAKeseler, 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 80:2939-2948.18331064Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Sokatch, John R.; Sanders, Lois E.; Marshall, Vincent P. Oxidation of methylmalonate semialdehyde to propionyl coenzyme A in Pseudomonas aeruginosa grown on valine. Journal of Biological Chemistry (1968), 243(10), 2500-6.Formate acetyltransferase 1P09373PFLB_ECOLIpflBhttp://ecmdb.ca/proteins/P09373.xmlPhosphate acetyltransferaseP0A9M8PTA_ECOLIptahttp://ecmdb.ca/proteins/P0A9M8.xmlPyruvate formate-lyase 1-activating enzymeP0A9N4PFLA_ECOLIpflAhttp://ecmdb.ca/proteins/P0A9N4.xml3-ketoacyl-CoA thiolaseP21151FADA_ECOLIfadAhttp://ecmdb.ca/proteins/P21151.xmlAcetyl-coenzyme A synthetaseP27550ACSA_ECOLIacshttp://ecmdb.ca/proteins/P27550.xml2-methylcitrate synthaseP31660PRPC_ECOLIprpChttp://ecmdb.ca/proteins/P31660.xmlFormate acetyltransferase 2P32674PFLD_ECOLIpflDhttp://ecmdb.ca/proteins/P32674.xmlKeto-acid formate acetyltransferaseP42632TDCE_ECOLItdcEhttp://ecmdb.ca/proteins/P42632.xmlMethylmalonyl-CoA decarboxylaseP52045MMCD_ECOLImmcDhttp://ecmdb.ca/proteins/P52045.xmlPutative formate acetyltransferase 3P75793PFLF_ECOLIybiWhttp://ecmdb.ca/proteins/P75793.xml3-ketoacyl-CoA thiolase_P76503FADI_ECOLIfadIhttp://ecmdb.ca/proteins/P76503.xmlPropionate--CoA ligaseP77495PRPE_ECOLIprpEhttp://ecmdb.ca/proteins/P77495.xmlUncharacterized protein ygfHP52043YGFH_ECOLIygfHhttp://ecmdb.ca/proteins/P52043.xmlAutonomous glycyl radical cofactorP68066GRCA_ECOLIgrcAhttp://ecmdb.ca/proteins/P68066.xmlWater + Oxalacetic acid + Propionyl-CoA <> Methylcitric acid + Coenzyme A + Hydrogen ion + (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylateR009312-METHYLCITRATE-SYNTHASE-RXNPhosphate + Propionyl-CoA > Coenzyme A + Propanoyl phosphateR00921PTAALT-RXNHydrogen ion + (S)-Methylmalonyl-CoA <> Carbon dioxide + Propionyl-CoAR00923Propionyl-CoA + Succinic acid > Propionic acid + Succinyl-CoARXN0-268Adenosine triphosphate + Coenzyme A + Propionic acid > ADP + Phosphate + Propionyl-CoAPropionyl-CoA + Phosphate <> Propanoyl phosphate + Coenzyme AR00921(S)-Methylmalonyl-CoA <> Propionyl-CoA + Carbon dioxideR00923Propinol adenylate + Coenzyme A <> Adenosine monophosphate + Propionyl-CoAR00926Propionyl-CoA + Acetyl-CoA <> Coenzyme A + 2-Methylacetoacetyl-CoAR00927Methylcitric acid + Coenzyme A <> Propionyl-CoA + Oxalacetic acid + WaterR00931Propionyl-CoA + Chenodeoxycholoyl-CoA <> Coenzyme A + 3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoAR045462-Ketobutyric acid + Coenzyme A <> Propionyl-CoA + Formic acidR06987Oxalacetic acid + Water + Propionyl-CoA <> Hydrogen ion + Methylcitric acid + Coenzyme A2-METHYLCITRATE-SYNTHASE-RXNPropionyl-CoA + Water + Glyoxylic acid <> 2-hydroxyglutarate + Hydrogen ion + Coenzyme AHYDGLUTSYN-RXN2-Ketobutyric acid + Coenzyme A > Propionyl-CoA + Formic acidKETOBUTFORMLY-RXNCoenzyme A + Propionic acid + Adenosine triphosphate > Propionyl-CoA + Pyrophosphate + Adenosine monophosphatePROPIONATE--COA-LIGASE-RXNAdenosine triphosphate + Hydrogen carbonate + Propionyl-CoA > Hydrogen ion + ADP + Phosphate + (S)-Methylmalonyl-CoAPROPIONYL-COA-CARBOXY-RXNPropionyl-CoA + Succinic acid <> Propionic acid + Succinyl-CoARXN0-268Hydrogen ion + R-Methylmalonyl-CoA > Propionyl-CoA + Carbon dioxideRXN0-310Propionyl-CoA + Water + Oxalacetic acid > (2R,3S)-2-Hydroxybutane-1,2,3-tricarboxylate + CoAAdenosine triphosphate + Propionic acid + CoA > Adenosine monophosphate + Pyrophosphate + Propionyl-CoA(S)-Methylmalonyl-CoA > Propionyl-CoA + Carbon dioxidePropionyl-CoA + Formic acid > CoA + 2-Ketobutyric acidPropionyl-CoA + NADP <> Acrylyl-CoA + NADPH + Hydrogen ionR00919 Adenosine triphosphate + Propionic acid + Coenzyme A <> Adenosine monophosphate + Pyrophosphate + Propionyl-CoAR00925 2-Ketobutyric acid + Coenzyme A > Formic acid + Propionyl-CoA + Propionyl-CoAPW_R003493Propionyl-CoA + Phosphate + Propionyl-CoA > Coenzyme A + propanoyl phosphate + Propanoyl phosphatePW_R003494Propionic acid + Adenosine triphosphate + Coenzyme A > Propionyl-CoA + Adenosine monophosphate + Pyrophosphate + Propionyl-CoAPW_R003496Propionyl-CoA + Water + Oxalacetic acid + Propionyl-CoA > Coenzyme A + Hydrogen ion + 2-Methylcitric acid + Methylcitric acidPW_R003497Succinic acid + Propionyl-CoA + Propionyl-CoA > Propionic acid + Succinyl-CoA + Succinyl-CoAPW_R003501Methylmalonyl-CoA + Hydrogen ion > Carbon dioxide + Propionyl-CoA + Propionyl-CoAPW_R003503R-Methylmalonyl-CoA + Hydrogen ion > Propionyl-CoA + Carbon dioxidePW_R006008Water + Oxalacetic acid + Propionyl-CoA <> Methylcitric acid + Coenzyme A + Hydrogen ion + (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylatePhosphate + Propionyl-CoA > Coenzyme A + Propanoyl phosphateGutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucoseShake flask and filter culture5.32uM0.037 oCK12 NCM3722Mid-Log Phase212800Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621