2.0 2012-05-31 10:26:56 -0600 2015-09-13 12:56:08 -0600 ECMDB00491 M2MDB000141 3-Methyl-2-oxovaleric acid 3-Methyl-2-oxovaleric acid is a metabolite of isoleucine in man, animals and bacteria. It is the alpha-keto acid analogue of isoleucine. 3-Methyl-2-oxovaleric acid is produced from isoleucine by cytosolic branched chain aminotransferase 1 (EC:2.6.1.42), whereupon it is further degraded by branched chain keto acid dehydrogenase E1 to 2-Methyl-1-hydroxybutyl-ThPP. &alpha;-keto-&beta;-methyl-valerate &alpha;-keto-&beta;-methyl-valeric acid &alpha;-keto-methylvalerate &alpha;-keto-methylvaleric acid (3<i>S</i>)-3-Methyl-2-oxopentanoate (3R)-3-Methyl-2-oxopentanoate (3R)-3-Methyl-2-oxopentanoic acid (3S)-3-Methyl-2-oxopentanoate (3S)-3-Methyl-2-oxopentanoic acid (<i>S</i>)-2-oxo-3-methylpentanoate (<i>S</i>)-3-methyl-2-oxopentanoate (R)-3-methyl-2-oxopentanoate (R)-3-methyl-2-oxopentanoic acid (S)-2-oxo-3-methylpentanoate (S)-2-oxo-3-methylpentanoic acid (S)-3-methyl-2-oxopentanoate (S)-3-methyl-2-oxopentanoic acid 2-Keto-3-methyl-valerate 2-Keto-3-methyl-valeric acid 2-keto-3-methylvalerate 2-keto-3-methylvaleric acid 2-Oxo-3-methyl-N-valerate 2-Oxo-3-methyl-N-valeric acid 2-Oxo-3-methylpentanoate 2-Oxo-3-methylpentanoic acid 2-Oxo-3-methylvalerate 2-Oxo-3-methylvaleric acid 2-Oxoisoleucine 2-Oxokolavenate 2-Oxokolavenic acid 2K3MVA 3-Methyl-2-oxo-pentanoate 3-Methyl-2-oxo-pentanoic acid 3-Methyl-2-oxo-Valerate 3-Methyl-2-oxo-Valeric acid 3-Methyl-2-oxopentanoate 3-Methyl-2-oxopentanoic acid 3-Methyl-2-oxovalerate 3-Methyl-2-oxovaleric A-Keto-b-Methyl-N-valerate A-Keto-b-Methyl-N-valeric acid a-keto-b-Methyl-valerate a-keto-b-Methyl-valeric acid A-Keto-b-methylvalerate A-Keto-b-methylvaleric acid a-keto-Methylvalerate a-keto-Methylvaleric acid A-Oxo-b-methyl-N-valerate A-Oxo-b-methyl-N-valeric acid A-Oxo-b-methylvalerate A-Oxo-b-methylvaleric acid Alpha-Keto-beta-Methyl-N-valerate Alpha-Keto-beta-Methyl-N-valeric acid Alpha-Keto-beta-methyl-valerate Alpha-Keto-beta-methyl-valeric acid Alpha-Keto-beta-methylvalerate Alpha-Keto-beta-methylvaleric acid Alpha-Keto-methylvalerate Alpha-Keto-methylvaleric acid Alpha-Oxo-beta-methyl-N-valerate Alpha-Oxo-beta-methyl-N-valeric acid Alpha-Oxo-beta-methylvalerate Alpha-Oxo-beta-methylvaleric acid α-keto-Methylvalerate α-keto-Methylvaleric acid α-keto-β-Methyl-N-valerate α-keto-β-Methyl-N-valeric acid α-keto-β-Methyl-valerate α-keto-β-Methyl-valeric acid α-keto-β-Methylvalerate α-keto-β-Methylvaleric acid α-oxo-β-Methyl-N-valerate α-oxo-β-Methyl-N-valeric acid α-oxo-β-Methylvalerate α-oxo-β-Methylvaleric acid C6H10O3 130.1418 130.062994186 3-methyl-2-oxopentanoic acid 3-methyl-2-oxopentanoic acid 1460-34-0 CCC(C)C(=O)C(O)=O InChI=1S/C6H10O3/c1-3-4(2)5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9) JVQYSWDUAOAHFM-UHFFFAOYSA-N Solid Cytosol logp 1.00 ALOGPS logs -1.12 ALOGPS solubility 9.86e+00 g/l ALOGPS logp 1.75 ChemAxon pka_strongest_acidic 3.52 ChemAxon pka_strongest_basic -9.7 ChemAxon iupac 3-methyl-2-oxopentanoic acid ChemAxon average_mass 130.1418 ChemAxon mono_mass 130.062994186 ChemAxon smiles CCC(C)C(=O)C(O)=O ChemAxon formula C6H10O3 ChemAxon inchi InChI=1S/C6H10O3/c1-3-4(2)5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9) ChemAxon inchikey JVQYSWDUAOAHFM-UHFFFAOYSA-N ChemAxon polar_surface_area 54.37 ChemAxon refractivity 31.79 ChemAxon polarizability 13.09 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 3 ChemAxon donor_count 1 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Valine, leucine and isoleucine biosynthesis ec00290 Valine, leucine and isoleucine degradation ec00280 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 Isoleucine biosynthesis begins with L-threonine from the threonine biosynthesis pathway. L-threonine interacts with a threonine dehydratase biosynthetic releasing water, a hydrogen ion and (2Z)-2-aminobut-2-enoate. This compound is isomerized into a 2-iminobutanoate which interacts with water and a hydrogen ion spontaneously, resulting in the release of ammonium and 2-ketobutyric acid. This compound reacts with pyruvic acid and hydrogen ion through an acetohydroxybutanoate synthase / acetolactate synthase 2 resulting in carbon dioxide and (S)-2-Aceto-2-hydroxybutanoic acid. The latter compound is reduced by an NADPH driven acetohydroxy acid isomeroreductase releasing NADP and acetohydroxy acid isomeroreductase. The latter compound is dehydrated by a dihydroxy acid dehydratase resulting in 3-methyl-2-oxovaleric acid.This compound reacts in a reversible reaction with L-glutamic acid through a Branched-chain-amino-acid aminotransferase resulting in oxoglutaric acid and L-isoleucine. L-isoleucine can also be transported into the cytoplasm through two different methods: a branched chain amino acid ABC transporter or a branched chain amino acid transporter BrnQ y. PW000818 Metabolic isoleucine biosynthesis I (from threonine) ILEUSYN-PWY Specdb::CMs 558 Specdb::CMs 559 Specdb::CMs 560 Specdb::CMs 561 Specdb::CMs 18742 Specdb::CMs 30071 Specdb::CMs 30072 Specdb::CMs 30327 Specdb::CMs 30328 Specdb::CMs 30580 Specdb::CMs 30581 Specdb::CMs 37566 Specdb::NmrOneD 1392 Specdb::NmrOneD 302785 Specdb::NmrOneD 302786 Specdb::NmrOneD 302787 Specdb::NmrOneD 302788 Specdb::NmrOneD 302789 Specdb::NmrOneD 302790 Specdb::NmrOneD 302791 Specdb::NmrOneD 302792 Specdb::NmrOneD 302793 Specdb::NmrOneD 302794 Specdb::NmrOneD 302795 Specdb::NmrOneD 302796 Specdb::NmrOneD 302797 Specdb::NmrOneD 302798 Specdb::NmrOneD 302799 Specdb::NmrOneD 302800 Specdb::NmrOneD 302801 Specdb::NmrOneD 302802 Specdb::NmrOneD 302803 Specdb::NmrOneD 302804 Specdb::MsMs 710 Specdb::MsMs 711 Specdb::MsMs 712 Specdb::MsMs 307627 Specdb::MsMs 307628 Specdb::MsMs 307629 Specdb::MsMs 351619 Specdb::MsMs 351620 Specdb::MsMs 351621 Specdb::MsMs 438616 Specdb::MsMs 438689 Specdb::NmrTwoD 1336 HMDB00491 439286 46 C03465 15614 2-KETO-3-METHYL-VALERATE Keseler, I. 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Kokai Tokkyo Koho (1979), 3 pp. http://hmdb.ca/system/metabolites/msds/000/000/410/original/HMDB00491.pdf?1358461718 Dihydroxy-acid dehydratase P05791 ILVD_ECOLI ilvD http://ecmdb.ca/proteins/P05791.xml 2-isopropylmalate synthase P09151 LEU1_ECOLI leuA http://ecmdb.ca/proteins/P09151.xml Branched-chain-amino-acid aminotransferase P0AB80 ILVE_ECOLI ilvE http://ecmdb.ca/proteins/P0AB80.xml alpha-Ketoglutarate + L-Isoleucine <> 3-Methyl-2-oxovaleric acid + L-Glutamate R02199 (R) 2,3-Dihydroxy-3-methylvalerate > 3-Methyl-2-oxovaleric acid + Water R05070 DIHYDROXYMETVALDEHYDRAT-RXN (R) 2,3-Dihydroxy-3-methylvalerate <> 3-Methyl-2-oxovaleric acid + Water R05070 L-Isoleucine + Oxoglutaric acid <> 3-Methyl-2-oxovaleric acid + L-Glutamate BRANCHED-CHAINAMINOTRANSFERILEU-RXN 3-Methyl-2-oxovaleric acid + L-Glutamic acid + 3-Methyl-2-oxovaleric acid + L-Glutamate > Oxoglutaric acid + L-Valine + L-Valine PW_R003714 3-Methyl-2-oxovaleric acid + Water + Acetyl-CoA + 3-Methyl-2-oxovaleric acid > Coenzyme A + Hydrogen ion + 2-Isopropylmalic acid PW_R002875 3-Methyl-2-oxovaleric acid + L-Glutamic acid + 3-Methyl-2-oxovaleric acid + L-Glutamate > Oxoglutaric acid + L-Isoleucine + L-Isoleucine PW_R002928 (R) 2,3-Dihydroxy-3-methylvalerate > Water + 3-Methyl-2-oxovaleric acid + 3-Methyl-2-oxovaleric acid PW_R002927 alpha-Ketoglutarate + L-Isoleucine <>3 3-Methyl-2-oxovaleric acid + L-Glutamate