2.02012-05-31 14:03:48 -06002015-06-03 15:54:41 -0600ECMDB04056M2MDB0005882,3-Dihydrodipicolinic acidL-2,3-Dihydrodipicolinate is involved in the lysine biosynthesis pathway. L-2,3-Dihydrodipicolinate is produced from a reaction between pyruvate and L-aspartate-semialdehyde, with water as a byproduct. The reaction is catalyzed by dihydrodipicolinate synthase. 2,3-Di-H-Dipicolinate2,3-Di-H-Dipicolinic acid2,3-Dihydrodipicolinate2,3-DPADihydrodipicolinateDihydrodipicolinic acidL-2,3-DihydrodipicolinateL-2,3-Dihydrodipicolinic acidC7H7NO4169.1348169.0375077172,3-dihydropyridine-2,6-dicarboxylic acid2,3-dihydrodipicolinic acid16052-12-3OC(=O)C1CC=CC(=N1)C(O)=OInChI=1S/C7H7NO4/c9-6(10)4-2-1-3-5(8-4)7(11)12/h1-2,5H,3H2,(H,9,10)(H,11,12)UWOCFOFVIBZJGH-UHFFFAOYSA-NSolidCytosollogp0.12logs-1.39solubility6.84e+00 g/lmelting_point135.2logp0.66pka_strongest_acidic3.17pka_strongest_basic-1.1iupac2,3-dihydropyridine-2,6-dicarboxylic acidaverage_mass169.1348mono_mass169.037507717smilesOC(=O)C1CC=CC(=N1)C(O)=OformulaC7H7NO4inchiInChI=1S/C7H7NO4/c9-6(10)4-2-1-3-5(8-4)7(11)12/h1-2,5H,3H2,(H,9,10)(H,11,12)inchikeyUWOCFOFVIBZJGH-UHFFFAOYSA-Npolar_surface_area86.96refractivity39.36polarizability15.08rotatable_bond_count2acceptor_count5donor_count2physiological_charge-2formal_charge0Lysine biosynthesisLysine is biosynthesized from L-aspartic acid. L-aspartic acid can be incorporated into the cell through various methods: C4 dicarboxylate / orotate:H+ symporter ,
glutamate / aspartate : H+ symporter GltP, dicarboxylate transporter , C4 dicarboxylate / C4 monocarboxylate transporter DauA, glutamate / aspartate ABC transporter
L-aspartic acid is phosphorylated by an ATP-driven Aspartate kinase resulting in ADP and L-aspartyl-4-phosphate. L-aspartyl-4-phosphate is then dehydrogenated through an NADPH driven aspartate semialdehyde dehydrogenase resulting in a release of phosphate, NADP and L-aspartic 4-semialdehyde (involved in methionine biosynthesis).
L-aspartic 4-semialdehyde interacts with a pyruvic acid through a 4-hydroxy-tetrahydrodipicolinate synthase resulting in a release of hydrogen ion, water and
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate. The latter compound is then reduced by an NADPH driven 4-hydroxy-tetrahydrodipicolinate reductase resulting in a release of water, NADP and (S)-2,3,4,5-tetrahydrodipicolinate, This compound interacts with succinyl-CoA and water through a tetrahydrodipicolinate succinylase resulting in a release of coenzyme A and N-Succinyl-2-amino-6-ketopimelate. This compound interacts with L-glutamic acid through a N-succinyldiaminopimelate aminotransferase resulting in oxoglutaric acid, N-succinyl-L,L-2,6-diaminopimelate. The latter compound is then desuccinylated by reacting with water through a N-succinyl-L-diaminopimelate desuccinylase resulting in a succinic acid and L,L-diaminopimelate. This compound is then isomerized through a diaminopimelate epimerase resulting in a meso-diaminopimelate (involved in peptidoglyccan biosynthesis I). This compound is then decarboxylated by a diaminopimelate decarboxylase resulting in a release of carbon dioxide and L-lysine.
L-lysine is then incorporated into lysine degradation pathway. Lysine also regulate its own biosynthesis by repressing dihydrodipicolinate synthase and also repressing lysine-sensitive aspartokinase 3.
A metabolic connection joins synthesis of an amino acid, lysine, to synthesis of cell wall material. Diaminopimelate is a precursor both for lysine and for cell wall components. The synthesis of lysine, methionine and threonine share two reactions at the start of the three pathways, the reactions converting L-aspartate to L-aspartate semialdehyde. The reaction involving aspartate kinase is carried out by three isozymes, one specific for synthesis of each end product amino acid. Each of the three aspartate kinase isozymes is regulated by its corresponding end product amino acid.PW000771ec00300MetabolicMicrobial metabolism in diverse environmentsec01120Secondary Metabolites: threonine biosynthesis from aspartateThe biosynthesis of threonine starts with L-aspartic acid being phosphorylated by an ATP driven Aspartate kinase resulting in an a release of an ADP and an L-aspartyl-4-phosphate. This compound interacts with a hydrogen ion through an NADPH driven aspartate semialdehyde dehydrogenase resulting in the release of a phosphate, an NADP and a L-aspartate-semialdehyde.The latter compound interacts with a hydrogen ion through a NADPH driven aspartate kinase / homoserine dehydrogenase resulting in the release of an NADP and a L-homoserine. L-homoserine is phosphorylated through an ATP driven homoserine kinase resulting in the release of an ADP, a hydrogen ion and a O-phosphohomoserine. The latter compound then interacts with a water molecule threonine synthase resulting in the release of a phosphate and an L-threonine. PW000976Metaboliclysine biosynthesis IDAPLYSINESYN-PWYSpecdb::CMs14882Specdb::CMs39883Specdb::CMs164885Specdb::NmrOneD96598Specdb::NmrOneD96599Specdb::NmrOneD96600Specdb::NmrOneD96601Specdb::NmrOneD96602Specdb::NmrOneD96603Specdb::NmrOneD96604Specdb::NmrOneD96605Specdb::NmrOneD96606Specdb::NmrOneD96607Specdb::NmrOneD96608Specdb::NmrOneD96609Specdb::NmrOneD96610Specdb::NmrOneD96611Specdb::NmrOneD96612Specdb::NmrOneD96613Specdb::NmrOneD96614Specdb::NmrOneD96615Specdb::NmrOneD96616Specdb::NmrOneD96617Specdb::MsMs32003Specdb::MsMs32004Specdb::MsMs32005Specdb::MsMs2443606Specdb::MsMs2443607Specdb::MsMs2443608Specdb::MsMs25445Specdb::MsMs25446Specdb::MsMs25447Specdb::MsMs2521989Specdb::MsMs2521990Specdb::MsMs2521991HMDB122471716C03340306202-3-DIHYDRODIPICOLINATEKeseler, 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 370:17-25.17765195Dihydrodipicolinate reductaseP04036DAPB_ECOLIdapBhttp://ecmdb.ca/proteins/P04036.xmlDihydrodipicolinate synthaseP0A6L2DAPA_ECOLIdapAhttp://ecmdb.ca/proteins/P0A6L2.xmlUncharacterized protein yjhHP39359YJHH_ECOLIyjhHhttp://ecmdb.ca/proteins/P39359.xmlUncharacterized protein yagEP75682YAGE_ECOLIyagEhttp://ecmdb.ca/proteins/P75682.xml2,3-Dihydrodipicolinic acid + Hydrogen ion + NADPH > NADP + TetrahydrodipicolinateR04199L-Aspartate-semialdehyde + Pyruvic acid > 2,3-Dihydrodipicolinic acid + Hydrogen ion +2 WaterR02292DIHYDRODIPICSYN-RXNL-Aspartate-semialdehyde + Pyruvic acid <> 2,3-Dihydrodipicolinic acid +2 WaterR02292Tetrahydrodipicolinate + NAD <> 2,3-Dihydrodipicolinic acid + NADH + Hydrogen ionR04198Tetrahydrodipicolinate + NADP <> 2,3-Dihydrodipicolinic acid + NADPH + Hydrogen ionR04199Pyruvic acid + L-Aspartate-semialdehyde <> Hydrogen ion + Water + 2,3-Dihydrodipicolinic acidDIHYDRODIPICSYN-RXNNAD(P)<sup>+</sup> + Tetrahydrodipicolinate < NAD(P)H + 2,3-Dihydrodipicolinic acid + Hydrogen ionDIHYDROPICRED-RXNL-Aspartate-semialdehyde + Pyruvic acid >2 2,3-Dihydrodipicolinic acid + Hydrogen ion +2 Water2 2,3-Dihydrodipicolinic acid + Hydrogen ion + NADPH > NADP + TetrahydrodipicolinateL-Aspartate-semialdehyde + Pyruvic acid >2 2,3-Dihydrodipicolinic acid + Hydrogen ion +2 Water