2.0 2012-05-31 14:21:15 -0600 2015-06-03 17:19:03 -0600 ECMDB12241 M2MDB000832 Isopropylmaleate Isopropylmaleate is an intermediate in branched chain amino acid metabolism (specifically L-leucine biosynthesis). It is a substrate for 3-isopropylmalate dehydratase. This enzyme catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. &beta;-isopropylmaleate &beta;-isopropylmaleic acid 2-Isopropylmaleate 2-Isopropylmaleic acid B-isopropylmaleate b-Isopropylmaleic acid Beta-Isopropylmaleate Beta-Isopropylmaleic acid Isopropylmaleic acid β-Isopropylmaleate β-Isopropylmaleic acid C7H10O4 158.1519 158.057908808 (2Z)-2-(propan-2-yl)but-2-enedioic acid 2-isopropylmaleic acid CC(C)C(=C\C(O)=O)\C(O)=O InChI=1S/C7H10O4/c1-4(2)5(7(10)11)3-6(8)9/h3-4H,1-2H3,(H,8,9)(H,10,11)/b5-3- NJMGRJLQRLFQQX-HYXAFXHYSA-N Solid Cytosol logp 1.05 ALOGPS logs -1.64 ALOGPS solubility 3.64e+00 g/l ALOGPS logp 1.09 ChemAxon pka_strongest_acidic 2.79 ChemAxon iupac (2Z)-2-(propan-2-yl)but-2-enedioic acid ChemAxon average_mass 158.1519 ChemAxon mono_mass 158.057908808 ChemAxon smiles CC(C)C(=C\C(O)=O)\C(O)=O ChemAxon formula C7H10O4 ChemAxon inchi InChI=1S/C7H10O4/c1-4(2)5(7(10)11)3-6(8)9/h3-4H,1-2H3,(H,8,9)(H,10,11)/b5-3- ChemAxon inchikey NJMGRJLQRLFQQX-HYXAFXHYSA-N ChemAxon polar_surface_area 74.6 ChemAxon refractivity 38.11 ChemAxon polarizability 15.11 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Valine, leucine and isoleucine biosynthesis ec00290 Metabolic pathways eco01100 Leucine Biosynthesis Leucine biosynthesis involves a five-step conversion process starting with the valine precursor 2-keto-isovalerate interacting with acetyl-CoA and water through a 2-isopropylmalate synthase resulting in Coenzyme A, hydrogen Ion and 2-isopropylmalic acid. The latter compound reacts with isopropylmalate isomerase which dehydrates the compound resulting in a Isopropylmaleate. This compound reacts with water through a isopropylmalate isomerase resulting in 3-isopropylmalate. This compound interacts with a NAD-driven D-malate / 3-isopropylmalate dehydrogenase results in 2-isopropyl-3-oxosuccinate. This compound interacts spontaneously with hydrogen resulting in the release of carbon dioxide and ketoleucine. Ketoleucine interacts in a reversible reaction with L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in Oxoglutaric acid and L-leucine L-leucine can then be exported outside the cytoplasm through a transporter: L-amino acid efflux transporter. The final step in this pathway is catalyzed by two transaminases of broad specificity, IlvE and TyrB. Both the first enzyme in the pathway, 2-isopropylmalate synthase, and the terminal transaminase TyrB are suppressed by leucine. TyrB is subject to inhibition by the pathway's starting compound, 2-keto-isovalerate, and by one of its off-pathway products, tyrosine. One consequence of this inhibition by 2-keto-isovalerate is that in the absence of IlvE activity, mutations in earlier steps in the pathway cannot be compensated for by any alternate method of introducing 2-ketoisocaproate for conversion to leucine. PW000811 Metabolic Secondary Metabolite: Leucine biosynthesis Leucine biosynthesis involves a five-step conversion process starting with a 3-methyl-2-oxovaleric acid interacting with acetyl-CoA and a water molecule through a 2-isopropylmalate synthase resulting in Coenzyme A, hydrogen Ion and 2-isopropylmalic acid. The latter compound reacts with isopropylmalate isomerase which dehydrates the compound resulting in a Isopropylmaleate. This compound reacts with water through a isopropylmalate isomerase resulting in 3-isopropylmalate. This compound interacts with a NAD-driven D-malate / 3-isopropylmalate dehydrogenase results in 2-isopropyl-3-oxosuccinate. This compound interacts spontaneously with hydrogen resulting in the release of carbon dioxide and ketoleucine. Ketoleucine interacts in a reversible reaction with L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in Oxoglutaric acid and L-leucine Both the first enzyme in the pathway, 2-isopropylmalate synthase, and the terminal transaminase TyrB are suppressed by leucine. TyrB is subject to inhibition by the pathway's starting compound, 2-keto-isovalerate, and by one of its off-pathway products, tyrosine. One consequence of this inhibition by 2-keto-isovalerate is that in the absence of IlvE activity, mutations in earlier steps in the pathway cannot be compensated for by any alternate method of introducing 2-ketoisocaproate for conversion to leucine. PW000980 Metabolic Secondary Metabolites: Valine and I-leucine biosynthesis from pyruvate The biosynthesis of Valine and L-leucine from pyruvic acid starts with pyruvic acid interacting with a hydrogen ion through a acetolactate synthase / acetohydroxybutanoate synthase resulting in a release of a carbon dioxide, a (S)-2-acetolactate. The latter compound then interacts with a hydrogen ion through a NADPH-driven acetohydroxy acid isomeroreductase resulting in the release of a NADP, a (R) 2,3-dihydroxy-3-methylvalerate. The latter compound is then dehydrated by a dihydroxy acid dehydratase resulting in the release of a water molecule an 3-methyl-2-oxovaleric acid. The 3-methyl-2-oxovaleric acid can produce an L-valine by interacting with a L-glutamic acid through a Valine Transaminase resulting in the release of a Oxoglutaric acid and a L-valine. The 3-methyl-2-oxovaleric acid then interacts with an acetyl-CoA and a water molecule through a 2-isopropylmalate synthase resulting in the release of a hydrogen ion, a Coenzyme A and a 2-Isopropylmalic acid. The isopropylimalic acid is then hydrated by interacting with a isopropylmalate isomerase resulting in a 3-isopropylmalate. This compound then interacts with an NAD driven 3-isopropylmalate dehydrogenase resulting in a NADH, a hydrogen ion and a 2-isopropyl-3-oxosuccinate. The latter compound then interacts with hydrogen ion spontaneously resulting in a carbon dioxide and a ketoleucine. The ketoleucine then interacts with a L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in the oxoglutaric acid and L-leucine. PW000978 Metabolic isoleucine biosynthesis I (from threonine) LEUSYN-PWY Specdb::CMs 3149 Specdb::CMs 39880 Specdb::CMs 156325 Specdb::NmrOneD 96538 Specdb::NmrOneD 96539 Specdb::NmrOneD 96540 Specdb::NmrOneD 96541 Specdb::NmrOneD 96542 Specdb::NmrOneD 96543 Specdb::NmrOneD 96544 Specdb::NmrOneD 96545 Specdb::NmrOneD 96546 Specdb::NmrOneD 96547 Specdb::NmrOneD 96548 Specdb::NmrOneD 96549 Specdb::NmrOneD 96550 Specdb::NmrOneD 96551 Specdb::NmrOneD 96552 Specdb::NmrOneD 96553 Specdb::NmrOneD 96554 Specdb::NmrOneD 96555 Specdb::NmrOneD 96556 Specdb::NmrOneD 96557 Specdb::MsMs 29228 Specdb::MsMs 29229 Specdb::MsMs 29230 Specdb::MsMs 35786 Specdb::MsMs 35787 Specdb::MsMs 35788 Specdb::MsMs 2702188 Specdb::MsMs 2702189 Specdb::MsMs 2702190 Specdb::MsMs 3006788 Specdb::MsMs 3006789 Specdb::MsMs 3006790 HMDB12241 230410 4444164 C02631 CPD-9451 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 Yurtsever D. (2007). Fatty acid methyl ester profiling of Enterococcus and Esherichia coli for microbial source tracking. M.sc. Thesis. Villanova University: U.S.A 3-isopropylmalate dehydratase large subunit P0A6A6 LEUC_ECOLI leuC http://ecmdb.ca/proteins/P0A6A6.xml 3-isopropylmalate dehydratase small subunit P30126 LEUD_ECOLI leuD http://ecmdb.ca/proteins/P30126.xml 3-Isopropylmalate <> Isopropylmaleate + Water R04001 RXN-8991 Isopropylmaleate + Water <> 2-Isopropylmalic acid R03968 2-Isopropylmalic acid <> Isopropylmaleate + Water R03968 3-Carboxy-3-hydroxy-isocaproate <> Isopropylmaleate + Water 3-ISOPROPYLMALISOM-RXN 3-Isopropylmalate < Isopropylmaleate + Water RXN-8991 3-Isopropylmalate > Isopropylmaleate + Water Isopropylmaleate + Water > 2-Isopropylmalic acid 3-Isopropylmalate + Isopropylmaleate + Water <> 2-Isopropylmalic acid R10170 2-Isopropylmalic acid > Water + Isopropylmaleate PW_R002876 Isopropylmaleate + Water > 3-Isopropylmalate PW_R002877 3 3-Isopropylmalate <> Isopropylmaleate + Water 3 3-Isopropylmalate <> Isopropylmaleate + Water