2.0 2012-05-31 14:06:45 -0600 2015-06-03 15:54:48 -0600 ECMDB04158 M2MDB000641 3-Isopropylmalate 3-Isopropylmalate is an intermediate in valine, leucine and isoleucine biosynthesis. It is a substrate for 3-isopropylmalate dehydrogenase (TT_C0867) &beta;-isopropylmalate &beta;-isopropylmalic acid (2R,3S)-2-hydroxy-3-(propan-2-yl)butanedioate (2R,3S)-2-hydroxy-3-(propan-2-yl)butanedioic acid (2R,3S)-2-hydroxy-3-isopropylsuccinate (2R,3S)-2-hydroxy-3-isopropylsuccinic acid (2R,3S)-3-carboxy-2-hydroxy-4-methylpentanoate (2R,3S)-3-carboxy-2-hydroxy-4-methylpentanoic acid (2R,3S)-3-Isopropylmalate (2R,3S)-3-isopropylmalic acid 2-D-Threo-Hydroxy-3-carboxy-isocaproate 2-D-Threo-Hydroxy-3-carboxy-isocaproic acid 2-D-Threo-hydroxy-3-carboxyisocaproate 2-D-Threo-hydroxy-3-carboxyisocaproic acid 3-3-Isopropylmalate 3-3-Isopropylmalic acid 3-Carboxy-2-hydroxy-4-methylpentanoate 3-Carboxy-2-hydroxy-4-methylpentanoic acid 3-isopropylmalate 3-Isopropylmalic acid 3IPMA b-Isopropylmalate b-Isopropylmalic acid Beta-Isopropylmalate Beta-Isopropylmalic acid IPM β-Isopropylmalate β-Isopropylmalic acid C7H12O5 176.1672 176.068473494 (2R,3S)-2-hydroxy-3-(propan-2-yl)butanedioic acid (2R,3S)-3-isopropylmalic acid 921-28-8 CC(C)[C@@H]([C@@H](O)C(O)=O)C(O)=O InChI=1S/C7H12O5/c1-3(2)4(6(9)10)5(8)7(11)12/h3-5,8H,1-2H3,(H,9,10)(H,11,12)/t4-,5+/m0/s1 RNQHMTFBUSSBJQ-CRCLSJGQSA-N Solid Outer membrane Inner membrane logp 0.28 ALOGPS logs -0.33 ALOGPS solubility 8.33e+01 g/l ALOGPS logp 0.16 ChemAxon pka_strongest_acidic 3.68 ChemAxon pka_strongest_basic -4 ChemAxon iupac (2R,3S)-2-hydroxy-3-(propan-2-yl)butanedioic acid ChemAxon average_mass 176.1672 ChemAxon mono_mass 176.068473494 ChemAxon smiles CC(C)[C@@H]([C@@H](O)C(O)=O)C(O)=O ChemAxon formula C7H12O5 ChemAxon inchi InChI=1S/C7H12O5/c1-3(2)4(6(9)10)5(8)7(11)12/h3-5,8H,1-2H3,(H,9,10)(H,11,12)/t4-,5+/m0/s1 ChemAxon inchikey RNQHMTFBUSSBJQ-CRCLSJGQSA-N ChemAxon polar_surface_area 94.83 ChemAxon refractivity 38.6 ChemAxon polarizability 16.47 ChemAxon rotatable_bond_count 4 ChemAxon acceptor_count 5 ChemAxon donor_count 3 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Valine, leucine and isoleucine biosynthesis ec00290 C5-Branched dibasic acid metabolism ec00660 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 3154 Specdb::CMs 32325 Specdb::CMs 39838 Specdb::CMs 100011 Specdb::CMs 151240 Specdb::NmrOneD 151350 Specdb::NmrOneD 151351 Specdb::NmrOneD 151352 Specdb::NmrOneD 151353 Specdb::NmrOneD 151354 Specdb::NmrOneD 151355 Specdb::NmrOneD 151356 Specdb::NmrOneD 151357 Specdb::NmrOneD 151358 Specdb::NmrOneD 151359 Specdb::NmrOneD 151360 Specdb::NmrOneD 151361 Specdb::NmrOneD 151362 Specdb::NmrOneD 151363 Specdb::NmrOneD 151364 Specdb::NmrOneD 151365 Specdb::NmrOneD 151366 Specdb::NmrOneD 151367 Specdb::NmrOneD 151368 Specdb::NmrOneD 151369 Specdb::MsMs 29375 Specdb::MsMs 29376 Specdb::MsMs 29377 Specdb::MsMs 35933 Specdb::MsMs 35934 Specdb::MsMs 35935 Specdb::MsMs 2733516 Specdb::MsMs 2733517 Specdb::MsMs 2733518 Specdb::MsMs 2972943 Specdb::MsMs 2972944 Specdb::MsMs 2972945 HMDB12156 5462261 4575349 C04411 35114 2-D-THREO-HYDROXY-3-CARBOXY-ISOCAPROATE IPM 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 3-isopropylmalate dehydratase large subunit P0A6A6 LEUC_ECOLI leuC http://ecmdb.ca/proteins/P0A6A6.xml 3-isopropylmalate dehydrogenase P30125 LEU3_ECOLI leuB http://ecmdb.ca/proteins/P30125.xml 3-isopropylmalate dehydratase small subunit P30126 LEUD_ECOLI leuD http://ecmdb.ca/proteins/P30126.xml D-malate dehydrogenase [decarboxylating] P76251 DMLA_ECOLI dmlA http://ecmdb.ca/proteins/P76251.xml 3-Isopropylmalate <> Isopropylmaleate + Water R04001 RXN-8991 3-Isopropylmalate + NAD > 2-Isopropyl-3-oxosuccinate + Hydrogen ion + NADH R04426 3-ISOPROPYLMALDEHYDROG-RXN 3-Isopropylmalate + NAD <> 2-Isopropyl-3-oxosuccinate + NADH + Hydrogen ion R04426 3-Isopropylmalate < Isopropylmaleate + Water RXN-8991 3-Isopropylmalate + NAD > Ketoleucine + Carbon dioxide + NADH 3-Isopropylmalate > Isopropylmaleate + Water 3-Isopropylmalate + Isopropylmaleate + Water <> 2-Isopropylmalic acid R10170 3-Isopropylmalate + NAD + 2-Isopropyl-3-oxosuccinate <> Ketoleucine + Carbon dioxide + NADH + Hydrogen ion R10052 Isopropylmaleate + Water > 3-Isopropylmalate PW_R002877 3 3-Isopropylmalate + NAD >2 2-Isopropyl-3-oxosuccinate + Hydrogen ion + NADH 3 3-Isopropylmalate <> Isopropylmaleate + Water 3 3-Isopropylmalate + NAD >2 2-Isopropyl-3-oxosuccinate + Hydrogen ion + NADH 3 3-Isopropylmalate <> Isopropylmaleate + Water