2.02012-05-31 14:03:10 -06002015-09-17 15:42:02 -0600ECMDB04043M2MDB0005762-Dehydropantoate2-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 acid2-Keto-pantoate2-Keto-pantoic acid2DHPAKetopantoateKetopantoic acidC6H9O4145.1333145.0500837764-hydroxy-3,3-dimethyl-2-oxobutanoic acidketopantoic acidCC(C)(CO)C(=O)C([O-])=OInChI=1S/C6H10O4/c1-6(2,3-7)4(8)5(9)10/h7H,3H2,1-2H3,(H,9,10)/p-1PKVVTUWHANFMQC-UHFFFAOYSA-MCytosollogp-0.35logs-0.13solubility1.09e+02 g/llogp0.58pka_strongest_acidic3.25pka_strongest_basic-2.8iupac4-hydroxy-3,3-dimethyl-2-oxobutanoic acidaverage_mass145.1333mono_mass145.050083776smilesCC(C)(CO)C(=O)C([O-])=OformulaC6H9O4inchiInChI=1S/C6H10O4/c1-6(2,3-7)4(8)5(9)10/h7H,3H2,1-2H3,(H,9,10)/p-1inchikeyPKVVTUWHANFMQC-UHFFFAOYSA-Mpolar_surface_area74.6refractivity33.47polarizability13.83rotatable_bond_count3acceptor_count4donor_count2physiological_charge-1formal_charge0Pantothenate and CoA biosynthesisThe 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].PW000828ec00770MetabolicMetabolic pathwayseco01100phosphopantothenate biosynthesis IPANTO-PWYSpecdb::CMs2946Specdb::NmrOneD311031Specdb::NmrOneD311032Specdb::NmrOneD311033Specdb::NmrOneD311034Specdb::NmrOneD311035Specdb::NmrOneD311036Specdb::NmrOneD311037Specdb::NmrOneD311038Specdb::NmrOneD311039Specdb::NmrOneD311040Specdb::NmrOneD311041Specdb::NmrOneD311042Specdb::NmrOneD311043Specdb::NmrOneD311044Specdb::NmrOneD311045Specdb::NmrOneD311046Specdb::NmrOneD311047Specdb::NmrOneD311048Specdb::NmrOneD311049Specdb::NmrOneD311050Specdb::MsMs20993Specdb::MsMs20994Specdb::MsMs20995Specdb::MsMs22544Specdb::MsMs22545Specdb::MsMs22546Specdb::MsMs3607915Specdb::MsMs3607916Specdb::MsMs3607917Specdb::MsMs3607918Specdb::MsMs3607919Specdb::MsMs36079203837C00966170942-DEHYDROPANTOATEKPLKeseler, 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-D590.21097882Kanehisa, 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-D114.22080510van 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 370:17-25.17765195Yurtsever D. (2007). Fatty acid methyl ester profiling of Enterococcus and Esherichia coli for microbial source tracking. M.sc. Thesis. Villanova University: U.S.AKetol-acid reductoisomeraseP05793ILVC_ECOLIilvChttp://ecmdb.ca/proteins/P05793.xml2-dehydropantoate 2-reductaseP0A9J4PANE_ECOLIpanEhttp://ecmdb.ca/proteins/P0A9J4.xml3-methyl-2-oxobutanoate hydroxymethyltransferaseP31057PANB_ECOLIpanBhttp://ecmdb.ca/proteins/P31057.xml2-Dehydropantoate + Hydrogen ion + NADPH <> NADP + (R)-PantoateR024722-DEHYDROPANTOATE-REDUCT-RXNalpha-Ketoisovaleric acid + Water + 5,10-Methylene-THF + a-Ketoisovaleric acid <> 2-Dehydropantoate + Tetrahydrofolic acidR012263-CH3-2-OXOBUTANOATE-OH-CH3-XFER-RXN5,10-Methylene-THF + alpha-Ketoisovaleric acid + Water <> Tetrahydrofolic acid + 2-DehydropantoateR01226(R)-Pantoate + NADP <> 2-Dehydropantoate + NADPH + Hydrogen ionR024722-DEHYDROPANTOATE-REDUCT-RXN(R)-Pantoate + NADP < Hydrogen ion + 2-Dehydropantoate + NADPH2-DEHYDROPANTOATE-REDUCT-RXN5,10-Methylene-THF + a-Ketoisovaleric acid + Water > Tetrahydrofolic acid + 2-Dehydropantoate(R)-Pantoate + NADP > 2-Dehydropantoate + NADPH2-dehydropantoate + NADPH + Hydrogen ion + 2-Dehydropantoate + NADPH > NADP + (R)-pantoate + (R)-PantoatePW_R003000a-Ketoisovaleric acid + 5,10-Methylene-THF + Water + 5,10-Methylene-THF > Tetrahydrofolic acid + 2-dehydropantoate + Tetrahydrofolic acid + 2-DehydropantoatePW_R0029992 2-Dehydropantoate + Hydrogen ion + NADPH <> NADP + (R)-Pantoatealpha-Ketoisovaleric acid + Water + 5 5,10-Methylene-THF + a-Ketoisovaleric acid <>2 2-Dehydropantoate + Tetrahydrofolic acid2 2-Dehydropantoate + Hydrogen ion + NADPH <> NADP + (R)-Pantoate