2.0 2012-05-31 14:03:10 -0600 2015-09-17 15:42:02 -0600 ECMDB04043 M2MDB000576 2-Dehydropantoate 2-dehydropantoate belongs to the class of Branched Fatty Acids. These are fatty acids containing a branched chain. (inferred from compound structure)2-dehydropantoate is invovled in Pantothenate and CoA biosynthesis, and Biosynthesis of secondary metabolites. (KEGG) 2-Dehydropantoic acid 2-Keto-pantoate 2-Keto-pantoic acid 2DHPA Ketopantoate Ketopantoic acid C6H9O4 145.1333 145.050083776 4-hydroxy-3,3-dimethyl-2-oxobutanoic acid ketopantoic acid CC(C)(CO)C(=O)C([O-])=O InChI=1S/C6H10O4/c1-6(2,3-7)4(8)5(9)10/h7H,3H2,1-2H3,(H,9,10)/p-1 PKVVTUWHANFMQC-UHFFFAOYSA-M Cytosol logp -0.35 ALOGPS logs -0.13 ALOGPS solubility 1.09e+02 g/l ALOGPS logp 0.58 ChemAxon pka_strongest_acidic 3.25 ChemAxon pka_strongest_basic -2.8 ChemAxon iupac 4-hydroxy-3,3-dimethyl-2-oxobutanoic acid ChemAxon average_mass 145.1333 ChemAxon mono_mass 145.050083776 ChemAxon smiles CC(C)(CO)C(=O)C([O-])=O ChemAxon formula C6H9O4 ChemAxon inchi InChI=1S/C6H10O4/c1-6(2,3-7)4(8)5(9)10/h7H,3H2,1-2H3,(H,9,10)/p-1 ChemAxon inchikey PKVVTUWHANFMQC-UHFFFAOYSA-M ChemAxon polar_surface_area 74.6 ChemAxon refractivity 33.47 ChemAxon polarizability 13.83 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon 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 phosphopantothenate biosynthesis I PANTO-PWY Specdb::CMs 2946 Specdb::NmrOneD 311031 Specdb::NmrOneD 311032 Specdb::NmrOneD 311033 Specdb::NmrOneD 311034 Specdb::NmrOneD 311035 Specdb::NmrOneD 311036 Specdb::NmrOneD 311037 Specdb::NmrOneD 311038 Specdb::NmrOneD 311039 Specdb::NmrOneD 311040 Specdb::NmrOneD 311041 Specdb::NmrOneD 311042 Specdb::NmrOneD 311043 Specdb::NmrOneD 311044 Specdb::NmrOneD 311045 Specdb::NmrOneD 311046 Specdb::NmrOneD 311047 Specdb::NmrOneD 311048 Specdb::NmrOneD 311049 Specdb::NmrOneD 311050 Specdb::MsMs 20993 Specdb::MsMs 20994 Specdb::MsMs 20995 Specdb::MsMs 22544 Specdb::MsMs 22545 Specdb::MsMs 22546 Specdb::MsMs 3607915 Specdb::MsMs 3607916 Specdb::MsMs 3607917 Specdb::MsMs 3607918 Specdb::MsMs 3607919 Specdb::MsMs 3607920 38 37 C00966 17094 2-DEHYDROPANTOATE KPL 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 Ketol-acid reductoisomerase P05793 ILVC_ECOLI ilvC http://ecmdb.ca/proteins/P05793.xml 2-dehydropantoate 2-reductase P0A9J4 PANE_ECOLI panE http://ecmdb.ca/proteins/P0A9J4.xml 3-methyl-2-oxobutanoate hydroxymethyltransferase P31057 PANB_ECOLI panB http://ecmdb.ca/proteins/P31057.xml 2-Dehydropantoate + Hydrogen ion + NADPH <> NADP + (R)-Pantoate R02472 2-DEHYDROPANTOATE-REDUCT-RXN alpha-Ketoisovaleric acid + Water + 5,10-Methylene-THF + a-Ketoisovaleric acid <> 2-Dehydropantoate + Tetrahydrofolic acid R01226 3-CH3-2-OXOBUTANOATE-OH-CH3-XFER-RXN 5,10-Methylene-THF + alpha-Ketoisovaleric acid + Water <> Tetrahydrofolic acid + 2-Dehydropantoate R01226 (R)-Pantoate + NADP <> 2-Dehydropantoate + NADPH + Hydrogen ion R02472 2-DEHYDROPANTOATE-REDUCT-RXN (R)-Pantoate + NADP < Hydrogen ion + 2-Dehydropantoate + NADPH 2-DEHYDROPANTOATE-REDUCT-RXN 5,10-Methylene-THF + a-Ketoisovaleric acid + Water > Tetrahydrofolic acid + 2-Dehydropantoate (R)-Pantoate + NADP > 2-Dehydropantoate + NADPH 2-dehydropantoate + NADPH + Hydrogen ion + 2-Dehydropantoate + NADPH > NADP + (R)-pantoate + (R)-Pantoate PW_R003000 a-Ketoisovaleric acid + 5,10-Methylene-THF + Water + 5,10-Methylene-THF > Tetrahydrofolic acid + 2-dehydropantoate + Tetrahydrofolic acid + 2-Dehydropantoate PW_R002999 2 2-Dehydropantoate + Hydrogen ion + NADPH <> NADP + (R)-Pantoate alpha-Ketoisovaleric acid + Water + 5 5,10-Methylene-THF + a-Ketoisovaleric acid <>2 2-Dehydropantoate + Tetrahydrofolic acid 2 2-Dehydropantoate + Hydrogen ion + NADPH <> NADP + (R)-Pantoate