2.02012-05-31 13:51:08 -06002015-09-13 12:56:11 -0600ECMDB01370M2MDB000360Diaminopimelic acidDiaminopimelic acid (DAP) is an amino acid, representing an epsilon-carboxy derivative of lysine. DAP found in the cell walls of E. coli and is a component of peptidoglycan of Gram-negative bacteria.( (R*,S*)-2,6-diamino-Heptanedioate( (R*,S*)-2,6-diamino-Heptanedioic acid(2R,6S)-2,6-diamino-heptanedioate(2R,6S)-2,6-diamino-heptanedioic acid(R*,S*)-2,6-diamino-Heptanedioate(R*,S*)-2,6-diamino-Heptanedioic acid2,6-Diamino-Heptanedioate2,6-Diamino-Heptanedioic acid2,6-Diaminoheptanedioate2,6-Diaminoheptanedioic acid2,6-Diaminopimelate2,6-Diaminopimelic acidA,a'-DiaminopimelateA,a'-Diaminopimelic acidA,e-DiaminopimelateA,e-Diaminopimelic acidD,L-DiaminopimelateD,L-Diaminopimelic acidD,L-Meso-diaminoheptanedioateD,L-Meso-diaminoheptanedioic acidDAPADiaminopimelateDiaminopimelic acidDl-2,6-DiaminoheptanedioateDl-2,6-Diaminoheptanedioic acidDL-2,6-DiaminopimelateDL-2,6-Diaminopimelic acidDPAL,L-2,6-DiaminoheptanedioateL,L-2,6-Diaminoheptanedioic acidL,L-2,6-DiaminopimelateL,L-2,6-Diaminopimelic acidL,L-A2pmL,L-DAPL,L-DiaminopimelateL,L-Diaminopimelic acidLL-2,6-diaminoheptanedioateLL-2,6-diaminoheptanedioic acidLL-2,6-DiaminopimelateLL-2,6-Diaminopimelic acidmeso-1-a,epsilon-Diaminopimelatemeso-1-a,epsilon-Diaminopimelic acidMeso-1-alpha,epsilon-diaminopimelateMeso-1-alpha,epsilon-diaminopimelic acidmeso-1-α,epsilon-Diaminopimelatemeso-1-α,epsilon-Diaminopimelic acidMeso-2,6-diamino-HeptanedioateMeso-2,6-diamino-Heptanedioic acidMeso-2,6-diaminoheptanedioateMeso-2,6-diaminoheptanedioic acidmeso-a,Alpha'-diaminopimelatemeso-a,Alpha'-diaminopimelic acidmeso-a,epsilon-Diaminopimelatemeso-a,epsilon-Diaminopimelic acidMeso-alpha,alpha'-DiaminopimelateMeso-alpha,alpha'-Diaminopimelic acidMeso-alpha,epsilon-DiaminopimelateMeso-alpha,epsilon-Diaminopimelic acidMeso-diaminoheptanedioateMeso-diaminoheptanedioic acidMeso-diaminopimelateMeso-diaminopimelic acidmeso-α,Alpha'-diaminopimelatemeso-α,Alpha'-diaminopimelic acidmeso-α,epsilon-Diaminopimelatemeso-α,epsilon-Diaminopimelic acidC7H14N2O4190.1971190.095356946(2S,6S)-2,6-diaminoheptanedioic aciddiamino-pimelic acid583-93-7N[C@@H](CCC[C@H](N)C(O)=O)C(O)=OInChI=1S/C7H14N2O4/c8-4(6(10)11)2-1-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5-/m0/s1GMKMEZVLHJARHF-WHFBIAKZSA-NSolidCytosolExtra-organismPeriplasmlogp-4.13logs-1.13solubility1.41e+01 g/lmelting_point300 oClogp-5.5pka_strongest_acidic1.85pka_strongest_basic9.83iupac(2S,6S)-2,6-diaminoheptanedioic acidaverage_mass190.1971mono_mass190.095356946smilesN[C@@H](CCC[C@H](N)C(O)=O)C(O)=OformulaC7H14N2O4inchiInChI=1S/C7H14N2O4/c8-4(6(10)11)2-1-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5-/m0/s1inchikeyGMKMEZVLHJARHF-WHFBIAKZSA-Npolar_surface_area126.64refractivity43.64polarizability18.93rotatable_bond_count6acceptor_count6donor_count4physiological_charge0formal_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 environmentsec01120Metabolic pathwayseco01100lysine biosynthesis IDAPLYSINESYN-PWYSpecdb::CMs731Specdb::CMs732Specdb::CMs2666Specdb::CMs30185Specdb::CMs30251Specdb::CMs38043Specdb::CMs170469Specdb::NmrOneD1690Specdb::NmrOneD147590Specdb::NmrOneD147591Specdb::NmrOneD147592Specdb::NmrOneD147593Specdb::NmrOneD147594Specdb::NmrOneD147595Specdb::NmrOneD147596Specdb::NmrOneD147597Specdb::NmrOneD147598Specdb::NmrOneD147599Specdb::NmrOneD147600Specdb::NmrOneD147601Specdb::NmrOneD147602Specdb::NmrOneD147603Specdb::NmrOneD147604Specdb::NmrOneD147605Specdb::NmrOneD147606Specdb::NmrOneD147607Specdb::NmrOneD147608Specdb::NmrOneD147609Specdb::MsMs1538Specdb::MsMs1539Specdb::MsMs1540Specdb::MsMs182697Specdb::MsMs182698Specdb::MsMs182699Specdb::MsMs183045Specdb::MsMs183046Specdb::MsMs183047Specdb::MsMs2240765Specdb::MsMs2240913Specdb::MsMs2244429Specdb::MsMs2244985Specdb::MsMs2245142Specdb::MsMs2245662Specdb::MsMs2246531Specdb::MsMs2247026Specdb::MsMs2247250Specdb::MsMs2247766Specdb::MsMs2249147Specdb::MsMs2249249Specdb::MsMs2251176Specdb::MsMs2251216Specdb::MsMs2330745Specdb::MsMs2330746Specdb::NmrTwoD1631HMDB01370865388416C0066623673LL-DIAMINOPIMELATEKeseler, 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 370:17-25.17765195Iida S, Taniguchi H, Kageyama A, Yazawa K, Chibana H, Murata S, Nomura F, Kroppenstedt RM, Mikami Y: Gordonia otitidis sp. nov., isolated from a patient with external otitis. Int J Syst Evol Microbiol. 2005 Sep;55(Pt 5):1871-6.16166681Ladesic B, Tomasic J, Kveder S, Hrsak I: The metabolic fate of 14C-labeled immunoadjuvant peptidoglycan monomer. II. In vitro studies. Biochim Biophys Acta. 1981 Nov 18;678(1):12-7.6118181Borruat G, Roten CA, Fay LB, Karamata D: A high-performance liquid chromatography method for the detection of diaminopimelic acid in urine. Anal Biochem. 2001 Apr 1;291(1):11-6.11262151Hamaker BR, Rivera K, Morales E, Graham GG: Effect of dietary fiber and starch on fecal composition in preschool children consuming maize, amaranth, or cassava flours. J Pediatr Gastroenterol Nutr. 1991 Jul;13(1):59-66.1656007Gao, Yong. Synthesis of diaminopimelic acid (DAP) and analogues: mechanistic studies on DAP aminotransferase, epimerase and dehydrogenase. (1998), 166 pp.http://hmdb.ca/system/metabolites/msds/000/001/232/original/HMDB01370.pdf?1358461364Diaminopimelate decarboxylaseP00861DCDA_ECOLIlysAhttp://ecmdb.ca/proteins/P00861.xmlDiaminopimelate epimeraseP0A6K1DAPF_ECOLIdapFhttp://ecmdb.ca/proteins/P0A6K1.xmlSuccinyl-diaminopimelate desuccinylaseP0AED7DAPE_ECOLIdapEhttp://ecmdb.ca/proteins/P0AED7.xmlUDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligaseP22188MURE_ECOLImurEhttp://ecmdb.ca/proteins/P22188.xmlProtein mpaAP0ACV6MPAA_ECOLImpaAhttp://ecmdb.ca/proteins/P0ACV6.xmlDiaminopimelate epimeraseP0A6K1DAPF_ECOLIdapFhttp://ecmdb.ca/proteins/P0A6K1.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlDiaminopimelic acid + Adenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamate > ADP + Hydrogen ion + Phosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminoheptanedioateL-alanine-D-glutamate-meso-2,6-diaminoheptanedioate + Water > Diaminopimelic acid + L-Alanyl-D-glutamateWater + N-Succinyl-L,L-2,6-diaminopimelate <> Diaminopimelic acid + Succinic acidR02734SUCCDIAMINOPIMDESUCC-RXNDiaminopimelic acid + Hydrogen ion > Carbon dioxide + L-LysineDiaminopimelic acid <> Meso-2,6-DiaminoheptanedioateR02735Diaminopimelic acid <> <i>meso</i>-diaminopimelateDIAMINOPIMEPIM-RXNN-succinyl-L-2,6-diaminoheptanedioate + Water > Succinic acid + Diaminopimelic acidDiaminopimelic acid > Meso-2,6-DiaminoheptanedioateN-Succinyl-L,L-2,6-diaminopimelate + Water > Succinic acid + Diaminopimelic acidPW_R002531Water + N-Succinyl-L,L-2,6-diaminopimelate <> Diaminopimelic acid + Succinic acid