2.0 2012-05-31 14:09:46 -0600 2015-06-03 15:54:55 -0600 ECMDB06855 M2MDB000697 (S)-2-Acetolactate (S)-2-Acetolactate is an intermediate in the biosynthesis of valine, leucine and isoleucine (KEGG ID C06010 ). It is the sixth to last step in the synthesis of protein and is converted from 2-hydroxy-3-methyl-2-oxobutanoate via the enzyme acetolactate synthase [EC:2.2.1.6]. It is then converted to 3-hydroxy-3-methyl-2-oxobutanoate via the enzyme ketol-acid reductoisomerase [EC:1.1.1.86]. (S)-2-Acetolactic acid (S)-2-Hydroxy-2-methyl-3-oxobutanoate (S)-2-Hydroxy-2-methyl-3-oxobutanoic acid 2-Ac C5H8O4 132.1146 132.042258744 (2S)-2-hydroxy-2-methyl-3-oxobutanoic acid acetolactic acid CC(=O)[C@](C)(O)C(O)=O InChI=1S/C5H8O4/c1-3(6)5(2,9)4(7)8/h9H,1-2H3,(H,7,8)/t5-/m0/s1 NMDWGEGFJUBKLB-YFKPBYRVSA-N Solid Cytosol logp -0.65 ALOGPS logs 0.33 ALOGPS solubility 2.86e+02 g/l ALOGPS logp -0.28 ChemAxon pka_strongest_acidic 3.45 ChemAxon pka_strongest_basic -4.6 ChemAxon iupac (2S)-2-hydroxy-2-methyl-3-oxobutanoic acid ChemAxon average_mass 132.1146 ChemAxon mono_mass 132.042258744 ChemAxon smiles CC(=O)[C@](C)(O)C(O)=O ChemAxon formula C5H8O4 ChemAxon inchi InChI=1S/C5H8O4/c1-3(6)5(2,9)4(7)8/h9H,1-2H3,(H,7,8)/t5-/m0/s1 ChemAxon inchikey NMDWGEGFJUBKLB-YFKPBYRVSA-N ChemAxon polar_surface_area 74.6 ChemAxon refractivity 28.59 ChemAxon polarizability 11.81 ChemAxon rotatable_bond_count 2 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Valine, leucine and isoleucine biosynthesis ec00290 C5-Branched dibasic acid metabolism ec00660 Pantothenate and CoA biosynthesis The CoA biosynthesis requires compounds from two other pathways: aspartate metabolism and valine biosynthesis. It requires a Beta-Alanine and R-pantoate. The compound (R)-pantoate is generated in two reactions, as shown by the interaction of alpha-ketoisovaleric acid, 5,10 methylene-THF and water through a 3-methyl-2-oxobutanoate hydroxymethyltransferase resulting in a tetrahydrofolic acid and a 2-dehydropantoate. This compound interacts with hydrogen through a NADPH driven acetohydroxy acid isomeroreductase resulting in the release of NADP and R-pantoate. On the other hand L-aspartic acid interacts with a hydrogen ion and gets decarboxylated through an Aspartate 1- decarboxylase resulting in a carbon dioxide and a Beta-alanine. Beta-alanine and R-pantoate interact with an ATP driven pantothenate synthetase resulting in pyrophosphate, AMP, hydrogen ion and pantothenic acid. Pantothenic acid is phosphorylated through a ATP-driven pantothenate kinase resulting in a ADP, a hydrogen ion and D-4'-Phosphopantothenate. This compound interacts with a CTP and a L-cysteine resulting in a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a hydrogen ion, a pyrophosphate, a CMP and 4-phosphopantothenoylcysteine. The latter compound interacts with a hydrogen ion through a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a carbon dioxide release and a 4-phosphopantetheine. This compound interacts with an ATP, hydrogen ion and an phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA. Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in a ADP , a hydrogen ion and a Coenzyme A. . The latter is converted into (R)-4'-phosphopantothenate is two steps, involving a β-alanine ligase and a kinase. In most organsims the ligase acts before the kinase (EC 6.3.2.1, pantoate—β-alanine ligase (AMP-forming) followed by EC 2.7.1.33, pantothenate kinase, as described in phosphopantothenate biosynthesis I and phosphopantothenate biosynthesis II. However, in archaea the order is reversed, and EC 2.7.1.169, pantoate kinase acts before EC 6.3.2.36, 4-phosphopantoate—β-alanine ligase, as described in phosphopantothenate biosynthesis III. The kinases are feedback inhibited by CoA itself, accounting for the primary regulatory mechanism of CoA biosynthesis. The addition of L-cysteine to (R)-4'-phosphopantothenate, resulting in the formation of R-4'-phosphopantothenoyl-L-cysteine (PPC), is followed by decarboxylation of PPC to 4'-phosphopantetheine. The ultimate reaction is catalyzed by EC 2.7.1.24, dephospho-CoA kinase, which converts 4'-phosphopantetheine to CoA. All enzymes of this pathway are essential for growth. The reactions in the biosynthetic route towards CoA are identical in most organisms, although there are differences in the functionality of the involved enzymes. In plants every step is catalyzed by single monofunctional enzymes, whereas in bacteria and mammals bifunctional enzymes are often employed [Rubio06]. PW000828 ec00770 Metabolic Metabolic pathways eco01100 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 Specdb::CMs 2638 Specdb::CMs 39122 Specdb::CMs 166112 Specdb::NmrOneD 91892 Specdb::NmrOneD 91893 Specdb::NmrOneD 91894 Specdb::NmrOneD 91895 Specdb::NmrOneD 91896 Specdb::NmrOneD 91897 Specdb::NmrOneD 91898 Specdb::NmrOneD 91899 Specdb::NmrOneD 91900 Specdb::NmrOneD 91901 Specdb::NmrOneD 91902 Specdb::NmrOneD 91903 Specdb::NmrOneD 91904 Specdb::NmrOneD 91905 Specdb::NmrOneD 91906 Specdb::NmrOneD 91907 Specdb::NmrOneD 91908 Specdb::NmrOneD 91909 Specdb::NmrOneD 91910 Specdb::NmrOneD 91911 Specdb::MsMs 23594 Specdb::MsMs 23595 Specdb::MsMs 23596 Specdb::MsMs 30392 Specdb::MsMs 30393 Specdb::MsMs 30394 Specdb::MsMs 2680518 Specdb::MsMs 2680519 Specdb::MsMs 2680520 Specdb::MsMs 3025401 Specdb::MsMs 3025402 Specdb::MsMs 3025403 HMDB06855 389710 C06010 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 Acetolactate synthase isozyme 3 large subunit P00893 ILVI_ECOLI ilvI http://ecmdb.ca/proteins/P00893.xml Acetolactate synthase isozyme 3 small subunit P00894 ILVH_ECOLI ilvH http://ecmdb.ca/proteins/P00894.xml Ketol-acid reductoisomerase P05793 ILVC_ECOLI ilvC http://ecmdb.ca/proteins/P05793.xml Acetolactate synthase isozyme 1 large subunit P08142 ILVB_ECOLI ilvB http://ecmdb.ca/proteins/P08142.xml Acetolactate synthase isozyme 1 small subunit P0ADF8 ILVN_ECOLI ilvN http://ecmdb.ca/proteins/P0ADF8.xml Acetolactate synthase isozyme 2 small subunit P0ADG1 ILVM_ECOLI ilvM http://ecmdb.ca/proteins/P0ADG1.xml Hydrogen ion + 2 Pyruvic acid > (S)-2-Acetolactate + Carbon dioxide R00226 (R)-2,3-Dihydroxy-isovalerate + NADP <> (S)-2-Acetolactate + Hydrogen ion + NADPH (S)-2-Acetolactate + Carbon dioxide <>2 Pyruvic acid R00226 (S)-2-Acetolactate + Thiamine pyrophosphate <> 2-(a-Hydroxyethyl)thiamine diphosphate + Pyruvic acid R04672 (S)-2-Acetolactate <> 3-Hydroxy-3-methyl-2-oxobutanoic acid R05071 (R)-2,3-Dihydroxy-isovalerate + NADP > (S)-2-Acetolactate + NADPH (S)-2-Acetolactate + Hydrogen ion + NADPH + NADPH > NADP + (R)-2,3-Dihydroxy-isovalerate PW_R005277