2.0 2012-05-31 13:00:45 -0600 2015-09-13 12:56:09 -0600 ECMDB00723 M2MDB000178 Methylcitric acid Methylcitric acid (MCA) is formed by condensation of accumulated propionyl- CoA and oxalacetate by the enzyme si-citrate synthase (EC 4.1.3.7). MCA molecule has two stereogenic centers so that it can occur in the form of four stereoisomers. (2<i>S</i>,3<i>S</i>)-2-hydroxybutane-1,2,3-tricarboxylate (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylic acid (2S,3S)-2-methylcitrate (2S,3S)-2-methylcitric acid 2-Hydroxy-1,2,3-butanetricarboxylate 2-Hydroxy-1,2,3-butanetricarboxylic acid 2-Hydroxybutane-1,2,3-tricarboxylate 2-Hydroxybutane-1,2,3-tricarboxylic acid 2-Methylcitrate 2-Methylcitric acid Methylcitrate C7H10O7 206.1501 206.042652674 2-hydroxy-1-methylpropane-1,2,3-tricarboxylic acid methylcitric acid 6061-96-7 CC(C(O)=O)C(O)(CC(O)=O)C(O)=O InChI=1S/C7H10O7/c1-3(5(10)11)7(14,6(12)13)2-4(8)9/h3,14H,2H2,1H3,(H,8,9)(H,10,11)(H,12,13) YNOXCRMFGMSKIJ-UHFFFAOYSA-N Solid Cytosol logp -0.89 ALOGPS logs -0.07 ALOGPS solubility 1.75e+02 g/l ALOGPS logp -0.78 ChemAxon pka_strongest_acidic 3.18 ChemAxon pka_strongest_basic -4.3 ChemAxon iupac 2-hydroxy-1-methylpropane-1,2,3-tricarboxylic acid ChemAxon average_mass 206.1501 ChemAxon mono_mass 206.042652674 ChemAxon smiles CC(C(O)=O)C(O)(CC(O)=O)C(O)=O ChemAxon formula C7H10O7 ChemAxon inchi InChI=1S/C7H10O7/c1-3(5(10)11)7(14,6(12)13)2-4(8)9/h3,14H,2H2,1H3,(H,8,9)(H,10,11)(H,12,13) ChemAxon inchikey YNOXCRMFGMSKIJ-UHFFFAOYSA-N ChemAxon polar_surface_area 132.13 ChemAxon refractivity 40.2 ChemAxon polarizability 17.21 ChemAxon rotatable_bond_count 5 ChemAxon acceptor_count 7 ChemAxon donor_count 4 ChemAxon physiological_charge -3 ChemAxon formal_charge 0 ChemAxon 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 2-methylcitrate cycle I PWY0-42 Specdb::CMs 19689 Specdb::CMs 37480 Specdb::CMs 168528 Specdb::CMs 1060058 Specdb::CMs 1060060 Specdb::CMs 1060062 Specdb::CMs 1060063 Specdb::CMs 1060064 Specdb::CMs 1060066 Specdb::CMs 1060068 Specdb::CMs 1060070 Specdb::CMs 1060072 Specdb::CMs 1060073 Specdb::CMs 1060075 Specdb::CMs 1060077 Specdb::CMs 1060079 Specdb::CMs 1060081 Specdb::CMs 1060083 Specdb::CMs 1060084 Specdb::CMs 1060086 Specdb::CMs 1060088 Specdb::CMs 1060090 Specdb::CMs 1060091 Specdb::CMs 1060093 Specdb::CMs 1060095 Specdb::NmrOneD 6682 Specdb::NmrOneD 6683 Specdb::NmrOneD 6684 Specdb::NmrOneD 6685 Specdb::NmrOneD 6686 Specdb::NmrOneD 6687 Specdb::NmrOneD 6688 Specdb::NmrOneD 6689 Specdb::NmrOneD 6690 Specdb::NmrOneD 6691 Specdb::NmrOneD 6692 Specdb::NmrOneD 6693 Specdb::NmrOneD 6694 Specdb::NmrOneD 6695 Specdb::NmrOneD 6696 Specdb::NmrOneD 6697 Specdb::NmrOneD 6698 Specdb::NmrOneD 6699 Specdb::NmrOneD 6700 Specdb::NmrOneD 6701 Specdb::MsMs 26378 Specdb::MsMs 26379 Specdb::MsMs 26380 Specdb::MsMs 32936 Specdb::MsMs 32937 Specdb::MsMs 32938 Specdb::MsMs 2283832 Specdb::MsMs 2283833 Specdb::MsMs 2283834 Specdb::MsMs 3081321 Specdb::MsMs 3081322 Specdb::MsMs 3081323 HMDB00379 515 500 C02225 30835 CPD-622 Keseler, I. 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(2007), 30pp. CODEN: PIXXD2 WO 2007101866 A2 20070913 CAN 147:363646 AN 20 http://hmdb.ca/system/metabolites/msds/000/000/298/original/HMDB00379.pdf?1358460264 2-methylcitrate synthase P31660 PRPC_ECOLI prpC http://ecmdb.ca/proteins/P31660.xml 2-methylcitrate dehydratase P77243 PRPD_ECOLI prpD http://ecmdb.ca/proteins/P77243.xml Water + Oxalacetic acid + Propionyl-CoA <> Methylcitric acid + Coenzyme A + Hydrogen ion + (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate R00931 2-METHYLCITRATE-SYNTHASE-RXN Methylcitric acid + (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate <> Cis-2-Methylaconitate + Water R04424 2-METHYLCITRATE-DEHYDRATASE-RXN Methylcitric acid + Coenzyme A <> Propionyl-CoA + Oxalacetic acid + Water R00931 Methylcitric acid <> Cis-2-Methylaconitate + Water R04424 Methylcitric acid > Water + Cis-2-Methylaconitate R04424 2-METHYLCITRATE-DEHYDRATASE-RXN Oxalacetic acid + Water + Propionyl-CoA <> Hydrogen ion + Methylcitric acid + Coenzyme A 2-METHYLCITRATE-SYNTHASE-RXN Propionyl-CoA + Water + Oxalacetic acid + Propionyl-CoA > Coenzyme A + Hydrogen ion + 2-Methylcitric acid + Methylcitric acid PW_R003497 2-Methylcitric acid + Methylcitric acid > Water + Cis-2-Methylaconitate PW_R003498 Methylcitric acid + (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate <> Cis-2-Methylaconitate + Water Water + Oxalacetic acid + Propionyl-CoA <> Methylcitric acid + Coenzyme A + Hydrogen ion + (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate Methylcitric acid + (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate <> Cis-2-Methylaconitate + Water