2.0 2012-05-31 13:55:02 -0600 2015-06-03 15:54:13 -0600 ECMDB02009 M2MDB000429 Crotonoyl-CoA Crotonoyl-CoA is an important component in several metabolic pathways, notably fatty acid and amino acid metabolism. It is the substrate of a group of enzymes acyl-Coenzyme A oxidases 1, 2, 3 (E.C.: 1.3.3.6) corresponding to palmitoyl, branched chain, and pristanoyl, respectively, in the peroxisomal fatty acid beta-oxidation, producing hydrogen peroxide. It is also a substrate of a group of enzymes called acyl-Coenzyme A dehydrogenase (E.C.:1.3.99-, including 1.3.99.2, 1.3.99.3) in the metabolism of fatty acids. In addition, crotonoyl-CoA is the substrate of enoyl coenzyme A hydratase (E.C.4.2.1.17) during lysine degradation and tryptophan metabolism, benzoate degradation via CoA ligation; in contrast it is the product of this enzyme in the butanoate metabolism. Moreover, it is produced from multiple enzymes in the butanoate metabolism pathway, including 3-Hydroxybutyryl-CoA dehydratase (E.C.:4.2.1.55), glutaconyl-CoA decarboxylase (E.C.: 4.1.1.70), vinylacetyl-CoA delta-isomerase (E.C.: 5.3.3.3), and trans-2-enoyl-CoA reductase (NAD+) (E.C.: 1.3.1.44). In lysine degradation and tryptophan metabolism, crotonoyl CoA is produced by glutaryl-Coenzyme A dehydrogenase (E.C.:1.3.99.7) lysine and tryptophan metabolic pathway. (E)-but-2-enoyl-CoA 2-Butenoyl-CoA 2-Butenoyl-Coenzyme A But-2-enoyl-CoA But-2-enoyl-Coenzyme A Crotonoyl-CoA Crotonyl-<i>S</i>-CoA Crotonyl-CoA Crotonyl-coenzyme A Crotonyl-S-CoA S-But-2-enoylcoenzyme A Trans-But-2-enoyl-CoA Trans-But-2-enoyl-Coenzyme A Trans-Butyr-2-enoyl-CoA C25H40N7O17P3S 835.608 835.141423115 {[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-2-{[({[(3-{[2-({2-[(2E)-but-2-enoylsulfanyl]ethyl}carbamoyl)ethyl]carbamoyl}-3-hydroxy-2,2-dimethylpropoxy)(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy}phosphonic acid [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-2-({[(3-{[2-({2-[(2E)-but-2-enoylsulfanyl]ethyl}carbamoyl)ethyl]carbamoyl}-3-hydroxy-2,2-dimethylpropoxy(hydroxy)phosphoryl)oxy(hydroxy)phosphoryl]oxy}methyl)-4-hydroxyoxolan-3-yl]oxyphosphonic acid 102680-35-3 C\C=C\C(=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=C(N)N=CN=C12 InChI=1S/C25H40N7O17P3S/c1-4-5-16(34)53-9-8-27-15(33)6-7-28-23(37)20(36)25(2,3)11-46-52(43,44)49-51(41,42)45-10-14-19(48-50(38,39)40)18(35)24(47-14)32-13-31-17-21(26)29-12-30-22(17)32/h4-5,12-14,18-20,24,35-36H,6-11H2,1-3H3,(H,27,33)(H,28,37)(H,41,42)(H,43,44)(H2,26,29,30)(H2,38,39,40)/b5-4+/t14-,18-,19-,20?,24-/m1/s1 KFWWCMJSYSSPSK-BOGFJHSMSA-N Solid Cytosol logp -0.11 ALOGPS logs -2.36 ALOGPS solubility 3.67e+00 g/l ALOGPS logp -5.6 ChemAxon pka_strongest_acidic 0.83 ChemAxon pka_strongest_basic 4.95 ChemAxon iupac {[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-2-{[({[(3-{[2-({2-[(2E)-but-2-enoylsulfanyl]ethyl}carbamoyl)ethyl]carbamoyl}-3-hydroxy-2,2-dimethylpropoxy)(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy}phosphonic acid ChemAxon average_mass 835.608 ChemAxon mono_mass 835.141423115 ChemAxon smiles C\C=C\C(=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=C(N)N=CN=C12 ChemAxon formula C25H40N7O17P3S ChemAxon inchi InChI=1S/C25H40N7O17P3S/c1-4-5-16(34)53-9-8-27-15(33)6-7-28-23(37)20(36)25(2,3)11-46-52(43,44)49-51(41,42)45-10-14-19(48-50(38,39)40)18(35)24(47-14)32-13-31-17-21(26)29-12-30-22(17)32/h4-5,12-14,18-20,24,35-36H,6-11H2,1-3H3,(H,27,33)(H,28,37)(H,41,42)(H,43,44)(H2,26,29,30)(H2,38,39,40)/b5-4+/t14-,18-,19-,20?,24-/m1/s1 ChemAxon inchikey KFWWCMJSYSSPSK-BOGFJHSMSA-N ChemAxon polar_surface_area 363.63 ChemAxon refractivity 182.53 ChemAxon polarizability 73.19 ChemAxon rotatable_bond_count 21 ChemAxon acceptor_count 17 ChemAxon donor_count 9 ChemAxon physiological_charge -4 ChemAxon formal_charge 0 ChemAxon Butanoate metabolism ec00650 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 Lysine degradation ec00310 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 1,4-Dichlorobenzene degradation ec00627 Microbial metabolism in diverse environments ec01120 Aminobenzoate Degradation Delete This pathway shows the various process by which various compounds reach Benzoate degradation. The top most reaction catalyzes (3s)-3-hydroxyacyl-Coa from crotonoyl-Coa and Water through 2,3-dehydroadipyl-CoA hydratase. The second reaction catalyzes Benzoic Acid from benzoyl phosphate through a weak acylphosphatase. The third reaction is 1,2,4 Benzenetriol which is catalyzed from 4-nitrocatechol through a predicted 2Fe-2s cluster-containing protein. This is a isomer of 4-nitrophenol which is produced from 4-phenylphosphate or 4-nitrophenylphosphate through a phosphoanhydride phosphorylase or alkaline phosphatase respectively The fourth reaction is the production of pyrocatechol from phenol, aniline or Nitrobenzene through a predicted 2Fe-2S cluster-containing protein. The fifth reaction is the production of (3s)-3 hydroxyacyl CoA from acetyl oa and 3-hydroxy-5-oxohexanoic through Acetate CoA-transferase (3s)-3-hydroxyacyl-Coa, Benzoic Acid, pyrocatechol and 1,2,4 Benzenetriol then go into Benzoate degradation. PW000757 Metabolic 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 Specdb::NmrOneD 333098 Specdb::NmrOneD 333099 Specdb::NmrOneD 333100 Specdb::NmrOneD 333101 Specdb::NmrOneD 333102 Specdb::NmrOneD 333103 Specdb::NmrOneD 333104 Specdb::NmrOneD 333105 Specdb::NmrOneD 333106 Specdb::NmrOneD 333107 Specdb::NmrOneD 333108 Specdb::NmrOneD 333109 Specdb::NmrOneD 333110 Specdb::NmrOneD 333111 Specdb::NmrOneD 333112 Specdb::NmrOneD 333113 Specdb::NmrOneD 333114 Specdb::NmrOneD 333115 Specdb::NmrOneD 333116 Specdb::NmrOneD 333117 Specdb::MsMs 24905 Specdb::MsMs 24906 Specdb::MsMs 24907 Specdb::MsMs 31463 Specdb::MsMs 31464 Specdb::MsMs 31465 HMDB02009 92856 4444072 C00877 15473 CROTONYL-COA Crotonyl-coenzyme A 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 Hyman DB, Tanaka K: Specific glutaryl-CoA dehydrogenating activity is deficient in cultured fibroblasts from glutaric aciduria patients. 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J Biol Chem. 1987 Jun 15;262(17):7982-9. 3597357 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 Fatty acid oxidation complex subunit alpha_ P77399 FADJ_ECOLI fadJ http://ecmdb.ca/proteins/P77399.xml Acyl-coenzyme A dehydrogenase Q47146 FADE_ECOLI fadE http://ecmdb.ca/proteins/Q47146.xml Fatty acid oxidation complex subunit alpha P21177 FADB_ECOLI fadB http://ecmdb.ca/proteins/P21177.xml 3-Hydroxybutyryl-CoA <> Crotonoyl-CoA + Water Butyryl-CoA + FAD <> Crotonoyl-CoA + FADH2 Butanoyl-CoA + FAD <> FADH2 + Crotonoyl-CoA R01175 (S)-3-Hydroxybutanoyl-CoA <> Crotonoyl-CoA + Water R03026 Crotonoyl-CoA + Water <> 3-Hydroxybutanoyl-CoA R05595 Crotonoyl-CoA + Water > (3S)-3-hydroxyacyl-CoA + (3S)-3-Hydroxyacyl-CoA PW_R002437 Crotonoyl-CoA > Water + 3-Hydroxybutyryl-CoA + 3-Hydroxybutyryl-CoA PW_R003768 3-Hydroxybutyryl-CoA + 3-Hydroxybutyryl-CoA <> Crotonoyl-CoA + Water PW_R002481 Butyryl-CoA + electron-transfer flavoprotein + Butyryl-CoA <> Crotonoyl-CoA + Reduced electron-transfer flavoprotein PW_R002480 Glutaryl-CoA > Crotonoyl-CoA + Carbon dioxide PW_R002483 3-Hydroxybutyryl-CoA + 3-Hydroxybutyryl-CoA > Crotonoyl-CoA PW_R003767