2.02012-05-31 13:48:00 -06002015-06-03 15:53:51 -0600ECMDB01228M2MDB000304L-Glutamic acid 5-phosphateL-Glutamic acid 5-phosphate is an intermediate in the urea cycle and metabolism of amino groups, a substrate of aldehyde dehydrogenase 18 family, member A1 [EC:2.7.2.11 1.2.1.41] (KEGG) Glu-5-PL-γ-glutamyl-5-PL-γ-glutamyl-5-phosphateL-γ-glutamyl-5-phosphoric acidL-g-Glutamyl-5-PL-g-Glutamyl-5-phosphateL-g-Glutamyl-5-phosphoric acidL-gamma-Glutamyl-5-PL-gamma-Glutamyl-5-phosphateL-gamma-Glutamyl-5-phosphoric acidL-Glutamate 5-phosphateL-Glutamate-5-phosphateL-Glutamic acid 5-phosphateL-Glutamic acid 5-phosphoric acidL-Glutamic acid-5-phosphoric acidL-Glutamyl 5-phosphateL-Glutamyl 5-phosphoric acidL-Glutamyl-5-PL-Glutamyl-5-phosphateL-Glutamyl-5-phosphoric acidL-γ-Glutamyl-5-PL-γ-Glutamyl-5-phosphateL-γ-Glutamyl-5-phosphoric acidC5H10NO7P227.1092227.019488191(2S)-2-amino-5-oxo-5-(phosphonooxy)pentanoic acidL-gamma-glutamyl phosphate13254-53-0N[C@@H](CCC(=O)OP(O)(O)=O)C(O)=OInChI=1S/C5H10NO7P/c6-3(5(8)9)1-2-4(7)13-14(10,11)12/h3H,1-2,6H2,(H,8,9)(H2,10,11,12)/t3-/m0/s1PJRXVIJAERNUIP-VKHMYHEASA-NSolidCytosollogp-1.96logs-1.32solubility1.09e+01 g/llogp-3pka_strongest_acidic1.12pka_strongest_basic9.51iupac(2S)-2-amino-5-oxo-5-(phosphonooxy)pentanoic acidaverage_mass227.1092mono_mass227.019488191smilesN[C@@H](CCC(=O)OP(O)(O)=O)C(O)=OformulaC5H10NO7PinchiInChI=1S/C5H10NO7P/c6-3(5(8)9)1-2-4(7)13-14(10,11)12/h3H,1-2,6H2,(H,8,9)(H2,10,11,12)/t3-/m0/s1inchikeyPJRXVIJAERNUIP-VKHMYHEASA-Npolar_surface_area147.15refractivity42.45polarizability18.09rotatable_bond_count6acceptor_count7donor_count4physiological_charge-2formal_charge0Arginine and proline metabolismec00330Metabolic pathwayseco01100proline metabolism
The biosynthesis of L-proline in E. coli involves L-glutamic acid being phosphorylated through an ATP driven glutamate 5-kinase resulting in a L-glutamic acid 5-phosphate. This compound is then reduced through a NADPH driven gamma glutamyl phosphate reductase resulting in the release of a phosphate, a NADP and a L-glutamic gamma-semialdehyde.
L-glutamic gamma-semialdehyde is dehydrated spontaneously, resulting in a release of water,hydrogen ion and 1-Pyrroline-5-carboxylic acid. The latter compound is reduced by an NADPH driven pyrroline-5-carboxylate reductase which is subsequently reduced to L-proline. L-proline works as a repressor of the pyrroline-5-carboxylate reductase enzyme and glutamate 5-kinase.
In E. coli, the biosynthesis of L-proline from L-glutamate is governed by three genetic loci namely proB, proA and proC. The first reaction in the pathway is catalyzed by γ-glutamyl kinase, encoded by proB . The second reaction, NADPH-dependent reduction of γ-glutamyl phosphate to glutamate-5-semialdehyde, in the pathway is catalyzed by glutamate-5-semialdehyde dehydrogenase, encoded by proA . These two enzymes aggregate into a multimeric bi-functional enzyme complex known as γ-glutamyl kinase-GP-reductase multienzyme complex. It is believed that the complex formation serves to protect the highly labile glutamyl phosphate from the hostile nucleophilic and aqueous environment found in the cell . The final step in the pathway, the reduction of pyrroline 5-carboxylate to L-proline, is catalyzed by an NADPH-dependent pyrroline-5-carboxylate reductase encoded by proC .
Proline is metabolized by being converted back to L-glutamate, which is further degraded to α-ketoglutarate, an intermediate of the TCA cycle. Curiously, L-glutamate, the obligate intermediate of the proline degradation pathway, cannot itself serve as a total source of carbon and energy for E. coli, because glutamate transport supplies exogenous glutamate at an inadequate rate.
The proces by which proline is turned into L-glutamate starts with L-proline interacting with ubiquinone through a bifunctional protein putA resulting in an ubiquinol, a hydrogen ion and a 1-pyrroline-5-carboxylic acid. The latter compound is then hydrated spontaneously resulting in a L-glutamic gamma-semialdehyde. This compound is then processed by interacting with water through an NAD driven bifunctional protein putA resulting in a hydrogen ion, NADH and L-glutamic acid.PW000794Metabolicproline biosynthesis IPROSYN-PWYSpecdb::CMs3258Specdb::CMs37983Specdb::CMs134135Specdb::CMs141869Specdb::NmrOneD87592Specdb::NmrOneD87593Specdb::NmrOneD87594Specdb::NmrOneD87595Specdb::NmrOneD87596Specdb::NmrOneD87597Specdb::NmrOneD87598Specdb::NmrOneD87599Specdb::NmrOneD87600Specdb::NmrOneD87601Specdb::NmrOneD87602Specdb::NmrOneD87603Specdb::NmrOneD87604Specdb::NmrOneD87605Specdb::NmrOneD87606Specdb::NmrOneD87607Specdb::NmrOneD87608Specdb::NmrOneD87609Specdb::NmrOneD87610Specdb::NmrOneD87611Specdb::MsMs29441Specdb::MsMs29442Specdb::MsMs29443Specdb::MsMs35999Specdb::MsMs36000Specdb::MsMs36001Specdb::MsMs2404523Specdb::MsMs2404524Specdb::MsMs2404525Specdb::MsMs2535063Specdb::MsMs2535064Specdb::MsMs2535065HMDB01228193475167893C03287L-GLUTAMATE-5-PKeseler, 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-D590.21097882van 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 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Journal of Heterocyclic Chemistry (1987), 24(1), 279-82.Gamma-glutamyl phosphate reductaseP07004PROA_ECOLIproAhttp://ecmdb.ca/proteins/P07004.xmlGlutamate 5-kinaseP0A7B5PROB_ECOLIproBhttp://ecmdb.ca/proteins/P0A7B5.xmlAdenosine triphosphate + L-Glutamate > ADP + L-Glutamic acid 5-phosphateGLUTKIN-RXNL-Glutamic acid 5-phosphate + Hydrogen ion + NADPH > L-Glutamic-gamma-semialdehyde + NADP + PhosphateGLUTSEMIALDEHYDROG-RXNL-Glutamic-gamma-semialdehyde + Phosphate + NADP < L-Glutamic acid 5-phosphate + NADPH + Hydrogen ionGLUTSEMIALDEHYDROG-RXNL-Glutamic-gamma-semialdehyde + Inorganic phosphate + NADP > L-Glutamic acid 5-phosphate + NADPHAdenosine triphosphate + L-Glutamate <> ADP + L-Glutamyl 5-phosphate + L-Glutamic acid 5-phosphateR00239L-Glutamic-gamma-semialdehyde + Phosphate + NADP <> L-Glutamyl 5-phosphate + NADPH + Hydrogen ion + L-Glutamic acid 5-phosphateR03313L-Glutamic acid 5-phosphate + Hydrogen ion + NADPH + NADPH > L-Glutamic-gamma-semialdehyde + NADP + PhosphatePW_R002716L-Glutamic-gamma-semialdehyde + Phosphate + NADP <> L-Glutamic acid 5-phosphate + NADPH + Hydrogen ionAdenosine triphosphate + L-Glutamate <> ADP + L-Glutamic acid 5-phosphateL-Glutamic-gamma-semialdehyde + Phosphate + NADP <> L-Glutamic acid 5-phosphate + NADPH + Hydrogen ionAdenosine triphosphate + L-Glutamate <> ADP + L-Glutamic acid 5-phosphate