2.0 2012-05-31 13:53:16 -0600 2015-09-17 15:41:12 -0600 ECMDB01484 M2MDB000397 Acetoacetyl-CoA Acetoacetyl-CoA is an intermediate in the metabolism of Butanoate. It is a substrate for Succinyl-CoA:3-ketoacid-coenzyme A transferase 1, Hydroxymethylglutaryl-CoA synthase , Short chain 3-hydroxyacyl-CoA dehydrogenase, Acetyl-CoA acetyltransferase, 3-hydroxyacyl-CoA dehydrogenase type , Succinyl-CoA:3-ketoacid-coenzyme A transferase 2, and 3-ketoacyl-CoA thiolase. 3-Acetoacetyl-CoA 3-Acetoacetyl-Coenzyme A 3-Oxobutyryl-CoA 3-Oxobutyryl-Coenzyme A Acetoacetyl coa Acetoacetyl coenzyme A Acetoacetyl-<i>S</i>-CoA Acetoacetyl-CoA Acetoacetyl-Coenzyme A Acetoacetyl-S-CoA S-Acetoacetylcoenzyme A C25H40N7O18P3S 851.607 851.136337737 {[(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-[(3-oxobutanoyl)sulfanyl]ethyl}carbamoyl)ethyl]carbamoyl}propoxy]phosphoryl}oxy)phosphoryl]oxy}methyl)oxolan-3-yl]oxy}phosphonic acid acetoacetyl-coa 1420-36-6 CC(=O)CC(=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=C2N InChI=1S/C25H40N7O18P3S/c1-13(33)8-16(35)54-7-6-27-15(34)4-5-28-23(38)20(37)25(2,3)10-47-53(44,45)50-52(42,43)46-9-14-19(49-51(39,40)41)18(36)24(48-14)32-12-31-17-21(26)29-11-30-22(17)32/h11-12,14,18-20,24,36-37H,4-10H2,1-3H3,(H,27,34)(H,28,38)(H,42,43)(H,44,45)(H2,26,29,30)(H2,39,40,41)/t14-,18-,19-,20?,24-/m1/s1 OJFDKHTZOUZBOS-XBTRWLRFSA-N Solid Cytosol logp -0.24 ALOGPS logs -2.16 ALOGPS solubility 5.84e+00 g/l ALOGPS logp -5.7 ChemAxon pka_strongest_acidic 0.82 ChemAxon pka_strongest_basic 4.01 ChemAxon iupac {[(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-[(3-oxobutanoyl)sulfanyl]ethyl}carbamoyl)ethyl]carbamoyl}propoxy]phosphoryl}oxy)phosphoryl]oxy}methyl)oxolan-3-yl]oxy}phosphonic acid ChemAxon average_mass 851.607 ChemAxon mono_mass 851.136337737 ChemAxon smiles CC(=O)CC(=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=C2N ChemAxon formula C25H40N7O18P3S ChemAxon inchi InChI=1S/C25H40N7O18P3S/c1-13(33)8-16(35)54-7-6-27-15(34)4-5-28-23(38)20(37)25(2,3)10-47-53(44,45)50-52(42,43)46-9-14-19(49-51(39,40)41)18(36)24(48-14)32-12-31-17-21(26)29-11-30-22(17)32/h11-12,14,18-20,24,36-37H,4-10H2,1-3H3,(H,27,34)(H,28,38)(H,42,43)(H,44,45)(H2,26,29,30)(H2,39,40,41)/t14-,18-,19-,20?,24-/m1/s1 ChemAxon inchikey OJFDKHTZOUZBOS-XBTRWLRFSA-N ChemAxon polar_surface_area 380.7 ChemAxon refractivity 182.1 ChemAxon polarizability 76.33 ChemAxon rotatable_bond_count 22 ChemAxon acceptor_count 18 ChemAxon donor_count 9 ChemAxon physiological_charge -4 ChemAxon formal_charge 0 ChemAxon Benzoate degradation via CoA ligation ec00632 Butanoate metabolism ec00650 Reductive carboxylate cycle (CO2 fixation) ec00720 Phenylalanine metabolism The pathways of the metabolism of phenylalaline begins with the conversion of chorismate to prephenate through a P-protein (chorismate mutase:pheA). Prephenate then interacts with a hydrogen ion through the same previous enzyme resulting in a release of carbon dioxide, water and a phenolpyruvic acid. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosine. Phenolpyruvic acid can also be obtained from a reversivle reaction with ammonia, a reduced acceptor and a D-amino acid dehydrogenase, resulting in a water, an acceptor and a D-phenylalanine, which can be then transported into the periplasmic space by aromatic amino acid exporter. L-phenylalanine also interacts in two reversible reactions, one involved with oxygen through a catalase peroxidase resulting in a carbon dioxide and 2-phenylacetamide. The other reaction involved an interaction with oxygen through a phenylalanine aminotransferase resulting in a oxoglutaric acid and phenylpyruvic acid. L-phenylalanine can be imported into the cytoplasm through an aromatic amino acid:H+ symporter AroP. The compound can also be imported into the periplasmic space through a transporter: L-amino acid efflux transporter. PW000921 ec00360 Metabolic Pyruvate metabolism ec00620 Tryptophan metabolism The biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan. The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoA PW000815 ec00380 Metabolic Glyoxylate and dicarboxylate metabolism ec00630 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 Lysine degradation ec00310 Valine, leucine and isoleucine degradation ec00280 Benzoate degradation via hydroxylation ec00362 Fatty acid metabolism This pathway depicts the degradation of palmitic acid (C16:0). Fatty acid degradation and synthesis are relatively simple processes that are essentially the reverse of each other. The process of fatty acid degradation, also known as Beta-Oxidation, converts an aliphatic compound into a set of activated acetyl units (acetyl CoA) that can be processed by the citric acid cycle. An activated fatty acid is first oxidized to introduce a double bond; the double bond is then hydrated to introduce an oxygen; the alcohol is then oxidized to a ketone; and, finally, the four carbon fragment is cleaved by coenzyme A to yield acetyl CoA and a fatty acid chain two carbons shorter. If the fatty acid has an even number of carbon atoms and is saturated, the process is simply repeated until the fatty acid is completely converted into acetyl CoA units. Fatty acid synthesis is essentially the reverse of this process. Because the result is a polymer, the process starts with monomers—in this case with activated acyl group and malonyl units. The malonyl unit is condensed with the acetyl unit to form a four-carbon fragment. To produce the required hydrocarbon chain, the carbonyl must be reduced. The fragment is reduced, dehydrated, and reduced again, exactly the opposite of degradation, to bring the carbonyl group to the level of a methylene group with the formation of butyryl CoA. Another activated malonyl group condenses with the butyryl unit and the process is repeated until a C16 fatty acid is synthesized. The first step converts the hydroxydecanoyl into a trans 2decenoyl acp through a protein complex conformed of a hydroxomyristoyl dehydratase and a hydroxydecanoyl dehydratase. The second step leads to the production of a cis 3 decenoyl acp through a 3-hydroxydecanoyl acp dehydratase. For the third step the cis 3 decenoyl acp enters a cycle involving a synthase, reductase, dehydratase and an enoyl reductase which in turn produce a cis x enoyl-acp, hydroxy cis x enoyl, trans x-2 cis x enoyl acp and cis x enoyl respectively.This is done until a palmitoleoyl is produce. In said case the pathway procedes in two different directions. It can either produce a palmitoleic acid through a acyl-coa thioesterase, or produce a Vaccenic acid through a different set of reactions. This process is achieved through a 3-oxoacyl acp synthase, a 3-oxoacyl acp reductase, a 3r hydroxymyristoyl dehydratase and an enoyl acp reductase that produces a transition through 3-oxo cis vaccenoyl acp, 3 hydroxy cis vaccenoyl acp, cis vaccen 2 enoyl acp and a cis vaccenoyl acp respectively. At this point it goes through one final reaction to produce a Vaccenic acid, through an acyl-CoA thioesterase PW000796 ec00071 Metabolic Terpenoid backbone biosynthesis ec00900 Synthesis and degradation of ketone bodies ec00072 Microbial metabolism in diverse environments ec01120 Metabolic pathways eco01100 fatty acid oxidation (Butanoate) Although enzymes of the pathway handle both short and long chain fatty acids, it is the long chain compounds that induce the enzymes of the pathway . Each turn of the cycle removes two carbon atoms until only two or three remain. When even-numbered fatty acids are broken down, a two-carbon compound remains, acetyl-CoA. When odd number fatty acids are broken down, a three-carbon residue results, propionylCoA. Unsaturated fatty acids, with cis double bonds located at odd-numbered carbon atoms, enter the main pathway of saturated fatty acid degradation by converting related metabolites of cis configuration and D stereoisomers, derived from breakdown of unsaturated fatty acids, to the trans- or L isomers of saturated fatty acid breakdown by an isomerase and an epimerase, respectively. When cis double bonds are located at even-numbered carbon atoms, such as linoleic acid (cis,cis(9,12)-octadecadienoic acid), after the fatty acid is degraded to the ten carbon stage an extra step is required to deal with the resulting compound, trans,δ(2)-cis,δ(4)decadienoyl-CoA. The enzyme 2,4-dienoyl-CoA reductase, converts this to trans,δ(2)decenoyl-CoA which enters the normal cycle at the point of the isomerase. The order of the reaction is as follows: a 2,3,4 saturated fatty acid is transformed into a 2,3,4 saturated fatty acyl CoA through a Long and short chain fatty acid CoA ligase. The 2,3,4 saturated fatty acyl CoA is then transformed into a trans 2 enoyl CoA. This enoyl can also be produced from a cis 3 enoyl CoA through a fatty acid oxidation protein complex. The trans 2 enoyl is transformed into a 3s 3 hydroxyacyl CoA through a 2,3 dehydroadipyl CoA hydratase. This same enzyme turns the product into a 3-oxoacyl-CoA. This is followed by the last step in the reaction when the oxoacyl-coa is turn into an acetyl coa+ a 2,3,4 saturated fatty acyl CoA through a 3-ketoacyl-CoA thiolase PW001017 Metabolic Acetate metabolism The acetate biosynthesis starts with acetyl-CoA reacting with phosphate through a phosphate acetyltransferase resulting in the release of a coenzyme A and an acetyl phosphate. The latter compound in turn reacts with ADP through an acetate kinase resulting in the release of an ATP and an acetate. The acetate reacts with ATP and coenzyme A through an acetyl-CoA synthase resulting in the release of a diphosphate, an AMP and an acetyl-CoA. Acetyl-CoA can be biosynthesized by acetoacetate reacting with an acetyl-CoA through an acetoacetyl-CoA transferase resulting in the release of an acetate and an acetoacetyl-CoA. The acetoacetyl-CoA reacts with an acetyl-CoA acetyltransferase resulting in the release of an coenzyme A and 2 acetyl-CoA PW002090 Metabolic acetoacetate degradation (to acetyl CoA) ACETOACETATE-DEG-PWY Specdb::NmrOneD 9422 Specdb::NmrOneD 9423 Specdb::NmrOneD 9424 Specdb::NmrOneD 9425 Specdb::NmrOneD 9426 Specdb::NmrOneD 9427 Specdb::NmrOneD 9428 Specdb::NmrOneD 9429 Specdb::NmrOneD 9430 Specdb::NmrOneD 9431 Specdb::NmrOneD 9432 Specdb::NmrOneD 9433 Specdb::NmrOneD 9434 Specdb::NmrOneD 9435 Specdb::NmrOneD 9436 Specdb::NmrOneD 9437 Specdb::NmrOneD 9438 Specdb::NmrOneD 9439 Specdb::NmrOneD 9440 Specdb::NmrOneD 9441 Specdb::MsMs 1471770 Specdb::MsMs 1471771 Specdb::MsMs 1471772 Specdb::MsMs 1471773 Specdb::MsMs 1471774 Specdb::MsMs 1471775 Specdb::MsMs 1471776 Specdb::MsMs 1471777 Specdb::MsMs 1471778 Specdb::MsMs 1471779 Specdb::MsMs 1471780 Specdb::MsMs 1471781 Specdb::MsMs 1471782 Specdb::MsMs 1471783 Specdb::MsMs 1471784 Specdb::MsMs 1471785 Specdb::MsMs 1471786 Specdb::MsMs 1471787 Specdb::MsMs 1471788 Specdb::MsMs 1471789 Specdb::MsMs 1471790 Specdb::MsMs 1471791 Specdb::MsMs 1475871 Specdb::MsMs 1475872 Specdb::MsMs 1475873 HMDB01484 439214 388353 C00332 15345 ACETOACETYL-COA CAA Acetoacetyl-CoA 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 Bennett, 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 3-ketoacyl-CoA thiolase P21151 FADA_ECOLI fadA http://ecmdb.ca/proteins/P21151.xml Fatty acid oxidation complex subunit alpha P21177 FADB_ECOLI fadB http://ecmdb.ca/proteins/P21177.xml Probable enoyl-CoA hydratase paaF P76082 PAAF_ECOLI paaF http://ecmdb.ca/proteins/P76082.xml Probable 3-hydroxybutyryl-CoA dehydrogenase P76083 PAAH_ECOLI paaH http://ecmdb.ca/proteins/P76083.xml Acetate CoA-transferase subunit alpha P76458 ATOD_ECOLI atoD http://ecmdb.ca/proteins/P76458.xml Acetate CoA-transferase subunit beta P76459 ATOA_ECOLI atoA http://ecmdb.ca/proteins/P76459.xml Acetyl-CoA acetyltransferase P76461 ATOB_ECOLI atoB http://ecmdb.ca/proteins/P76461.xml 3-ketoacyl-CoA thiolase_ P76503 FADI_ECOLI fadI http://ecmdb.ca/proteins/P76503.xml Fatty acid oxidation complex subunit alpha_ P77399 FADJ_ECOLI fadJ http://ecmdb.ca/proteins/P77399.xml Probable acetyl-CoA acetyltransferase Q46939 YQEF_ECOLI yqeF http://ecmdb.ca/proteins/Q46939.xml Fatty acid oxidation complex subunit alpha P21177 FADB_ECOLI fadB http://ecmdb.ca/proteins/P21177.xml Acetoacetic acid + Acetyl-CoA > Acetoacetyl-CoA + Acetic acid R01359 ACETOACETYL-COA-TRANSFER-RXN 2 Acetyl-CoA <> Acetoacetyl-CoA + Coenzyme A R00238 ACETYL-COA-ACETYLTRANSFER-RXN Acetoacetyl-CoA + Hydrogen ion + NADH <> 3-Hydroxybutyryl-CoA + NAD Acetoacetyl-CoA + Acetic acid <> Acetoacetic acid + Acetyl-CoA R01359 (S)-3-Hydroxybutanoyl-CoA + NAD <> Acetoacetyl-CoA + NADH + Hydrogen ion R01975 (S)-3-Hydroxybutanoyl-CoA + NADP + 3-Hydroxybutyryl-CoA <> Acetoacetyl-CoA + NADPH + Hydrogen ion R01976 3-Hydroxybutanoyl-CoA + NADP <> Acetoacetyl-CoA + NADPH + Hydrogen ion R05576 Acetoacetic acid + Acetyl-CoA <> Acetoacetyl-CoA + Acetic acid ACETOACETYL-COA-TRANSFER-RXN Acetyl-CoA <> Acetoacetyl-CoA + Coenzyme A ACETYL-COA-ACETYLTRANSFER-RXN 2 Acetyl-CoA > CoA + Acetoacetyl-CoA 3-Hydroxybutyryl-CoA + NADP > Acetoacetyl-CoA + NADPH 3-Hydroxybutyryl-CoA + NAD + 3-Hydroxybutyryl-CoA > NADH + Hydrogen ion + Acetoacetyl-CoA + Acetoacetyl-CoA PW_R003769 Acetoacetyl-CoA + Coenzyme A + Acetoacetyl-CoA > Acetyl-CoA + Succinyl-CoA + Succinyl-CoA PW_R003770 3-Hydroxybutyryl-CoA + NAD + 3-Hydroxybutyryl-CoA <> Acetoacetyl-CoA + NADH + Hydrogen ion + Acetoacetyl-CoA PW_R002484 2 Acetyl-CoA <> Acetoacetyl-CoA + Coenzyme A + Acetoacetyl-CoA PW_R002482 Acetoacetyl-CoA > Coenzyme A + Acetyl-CoA PW_R006101 2 Acetyl-CoA <> Acetoacetyl-CoA + Coenzyme A 2 Acetyl-CoA <> Acetoacetyl-CoA + Coenzyme A Gutnick 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 glucose Shake flask and filter culture 21.8 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 87200 0 Bennett, 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