2.0 2012-05-31 14:20:42 -0600 2015-06-03 17:19:02 -0600 ECMDB12140 M2MDB000822 (R) 2,3-Dihydroxy-3-methylvalerate (R) 2,3-Dihydroxy-methylvalerate is an intermediate in valine, leucine and isoleucine biosynthesis. The pathway of valine biosynthesis is a four-step pathway that shares all of its steps with the parallel pathway of isoleucine biosynthesis. These entwined pathways are part of the superpathway of leucine, valine, and isoleucine biosynthesis, that generates not only isoleucine and valine, but also leucine. (R) 2,3-Dihydroxy-methylvalerate is generated from 3-Hydroxy-3-methyl-2-oxopentanoic acid via the enzyme ketol-acid reductoisomerase (EC 1.1.1.86) then it is converted to (S)-3-methyl-2-oxopentanoic via the dihydroxy-acid dehydratase (EC:4.2.1.9). (2R,3R)-2,3-dihydroxy-3-methylpentanoate (2R,3R)-2,3-dihydroxy-3-methylpentanoic acid (R) 2,3-Dihydroxy-3-methylvaleric acid (R)-2,3-Dihydroxy-3-methylpentanoate (R)-2,3-Dihydroxy-3-methylpentanoic acid (R)-2,3-Dihydroxy-3-methylvalerate (R)-2,3-Dihydroxy-3-methylvaleric acid 1-Keto-2-methylvalerate 1-Keto-2-methylvaleric acid 2,3-Dihydroxy-3-Methyl-Valerate 2,3-Dihydroxy-3-Methyl-Valeric acid 2,3-Dihydroxy-3-methylpentanoate 2,3-Dihydroxy-3-methylpentanoic acid 2,3-Dihydroxy-Valerianate 2,3-Dihydroxy-Valerianic Acid 4,5-Dideoxy-3-C-methyl-pentonate 4,5-Dideoxy-3-C-methyl-pentonic acid a,b-Dihydroxy-b-methylvalerate a,b-Dihydroxy-b-methylvaleric acid Alpha,beta-Dihydroxy-beta-methylvalerate Alpha,beta-Dihydroxy-beta-methylvaleric acid CID8 DMV α,β-Dihydroxy-β-methylvalerate α,β-Dihydroxy-β-methylvaleric acid C6H12O4 148.1571 148.073558872 (2R,3R)-2,3-dihydroxy-3-methylpentanoic acid (2R,3R)-2,3-dihydroxy-3-methylpentanoic acid 562-43-6 CC[C@@](C)(O)[C@@H](O)C(O)=O InChI=1S/C6H12O4/c1-3-6(2,10)4(7)5(8)9/h4,7,10H,3H2,1-2H3,(H,8,9)/t4-,6+/m0/s1 PDGXJDXVGMHUIR-UJURSFKZSA-N Solid Cytosol logp -0.44 ALOGPS logs 0.52 ALOGPS solubility 4.86e+02 g/l ALOGPS logp -0.3 ChemAxon pka_strongest_acidic 3.93 ChemAxon pka_strongest_basic -3.3 ChemAxon iupac (2R,3R)-2,3-dihydroxy-3-methylpentanoic acid ChemAxon average_mass 148.1571 ChemAxon mono_mass 148.073558872 ChemAxon smiles CC[C@@](C)(O)[C@@H](O)C(O)=O ChemAxon formula C6H12O4 ChemAxon inchi InChI=1S/C6H12O4/c1-3-6(2,10)4(7)5(8)9/h4,7,10H,3H2,1-2H3,(H,8,9)/t4-,6+/m0/s1 ChemAxon inchikey PDGXJDXVGMHUIR-UJURSFKZSA-N ChemAxon polar_surface_area 77.76 ChemAxon refractivity 33.96 ChemAxon polarizability 14.43 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 4 ChemAxon donor_count 3 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Valine, leucine and isoleucine biosynthesis ec00290 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 Valine Biosynthesis The pathway of valine biosynthesis starts with pyruvic acid interacting with a hydrogen ion through a acetolactate synthase / acetohydroxybutanoate synthase or a acetohydroxybutanoate synthase / acetolactate synthase resulting in the release of carbon dioxide and (S)-2-acetolactate. The latter compound then interacts with a hydrogen ion through an NADPH driven acetohydroxy acid isomeroreductase resulting in the release of a NADP and an (R) 2,3-dihydroxy-3-methylvalerate. The latter compound is then dehydrated by a dihydroxy acid dehydratase resulting in the release of water and isovaleric acid. Isovaleric acid interacts with an L-glutamic acid through a Valine Transaminase resulting in a oxoglutaric acid and an L-valine. L-valine is then transported into the periplasmic space through a L-valine efflux transporter. PW000812 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 3265 Specdb::CMs 39826 Specdb::CMs 136746 Specdb::CMs 144480 Specdb::NmrOneD 151230 Specdb::NmrOneD 151231 Specdb::NmrOneD 151232 Specdb::NmrOneD 151233 Specdb::NmrOneD 151234 Specdb::NmrOneD 151235 Specdb::NmrOneD 151236 Specdb::NmrOneD 151237 Specdb::NmrOneD 151238 Specdb::NmrOneD 151239 Specdb::NmrOneD 151240 Specdb::NmrOneD 151241 Specdb::NmrOneD 151242 Specdb::NmrOneD 151243 Specdb::NmrOneD 151244 Specdb::NmrOneD 151245 Specdb::NmrOneD 151246 Specdb::NmrOneD 151247 Specdb::NmrOneD 151248 Specdb::NmrOneD 151249 Specdb::MsMs 24485 Specdb::MsMs 24486 Specdb::MsMs 24487 Specdb::MsMs 31043 Specdb::MsMs 31044 Specdb::MsMs 31045 Specdb::MsMs 3051032 Specdb::MsMs 3051033 Specdb::MsMs 3051034 Specdb::MsMs 3119320 Specdb::MsMs 3119321 Specdb::MsMs 3119322 HMDB12140 448154 395044 C06007 27512 1-KETO-2-METHYLVALERATE DMV 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 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 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 Dihydroxy-acid dehydratase P05791 ILVD_ECOLI ilvD http://ecmdb.ca/proteins/P05791.xml Ketol-acid reductoisomerase P05793 ILVC_ECOLI ilvC http://ecmdb.ca/proteins/P05793.xml (R) 2,3-Dihydroxy-3-methylvalerate > 3-Methyl-2-oxovaleric acid + Water R05070 DIHYDROXYMETVALDEHYDRAT-RXN 2-Aceto-2-hydroxy-butyrate + Hydrogen ion + NADPH <> (R) 2,3-Dihydroxy-3-methylvalerate + NADP ACETOOHBUTREDUCTOISOM-RXN (R) 2,3-Dihydroxy-3-methylvalerate + NADP <> (R)-3-Hydroxy-3-methyl-2-oxopentanoate + NADPH + Hydrogen ion R05068 (R) 2,3-Dihydroxy-3-methylvalerate <> 3-Methyl-2-oxovaleric acid + Water R05070 (R) 2,3-Dihydroxy-3-methylvalerate + NADP <> Hydrogen ion + 2-Aceto-2-hydroxy-butyrate + NADPH ACETOOHBUTREDUCTOISOM-RXN (R) 2,3-Dihydroxy-3-methylvalerate + NADP > 2-Aceto-2-hydroxy-butyrate + NADPH (R)-2,3-Dihydroxy-isovalerate + Hydrogen ion + NADPH + NADPH > NADP + (R) 2,3-Dihydroxy-3-methylvalerate PW_R002884 2-Aceto-2-hydroxy-butyrate + NADPH + Hydrogen ion + NADPH > NADP + (R) 2,3-Dihydroxy-3-methylvalerate PW_R002926 (R) 2,3-Dihydroxy-3-methylvalerate > Water + 3-Methyl-2-oxovaleric acid + 3-Methyl-2-oxovaleric acid PW_R002927