2.0 2012-05-31 13:49:31 -0600 2015-06-03 15:53:55 -0600 ECMDB01305 M2MDB000331 L-Glutamic-gamma-semialdehyde Glutamic gamma-semialdehyde is the metabolic precursor for proline biosynthesis. The conversion from L-Glutamate, an ATP- and NADPH-dependent reaction, is catalyzed by the enzyme Delta-1-pyrroline-5-carboxylate synthetase (P5CS) (OMIM 138250). L-Glutamic-gamma-semialdehyde can also be converted to or be formed from the amino acids L-ornithine (EC 2.6.1.13) and L-proline (EC 1.5.99.8 and EC 1.5.1.2). It is also one of the few metabolites that can be a precursor to other metabolites of both the urea cycle and the citric acid cycle (BioCyc) Glutamate-semialdehyde Glutamic &gamma;-semialdehyde Glutamic acid-semialdehyde Glutamic g-semialdehyde Glutamic gamma-semialdehyde Glutamic γ-semialdehyde L-Glutamate 5-semialdehyde L-Glutamate g-semialdehyde L-Glutamate gamma-semialdehyde L-Glutamate γ-semialdehyde L-Glutamate-5-semialdehyde L-Glutamic acid 5-semialdehyde L-Glutamic acid g-semialdehyde L-Glutamic acid gamma-semialdehyde L-Glutamic acid γ-semialdehyde L-Glutamic acid-5-semialdehyde L-Glutamic-g-semialdehyde L-Glutamic-gamma-semialdehyde L-Glutamic-γ-semialdehyde C5H9NO3 131.1299 131.058243159 (2S)-2-amino-5-oxopentanoic acid 4-carboxy-4-aminobutanal 496-92-4 N[C@@H](CCC=O)C(O)=O InChI=1S/C5H9NO3/c6-4(5(8)9)2-1-3-7/h3-4H,1-2,6H2,(H,8,9)/t4-/m0/s1 KABXUUFDPUOJMW-BYPYZUCNSA-N Solid Cytosol logp -2.57 ALOGPS logs 0.04 ALOGPS solubility 1.44e+02 g/l ALOGPS logp -3.4 ChemAxon pka_strongest_acidic 2.12 ChemAxon pka_strongest_basic 9.11 ChemAxon iupac (2S)-2-amino-5-oxopentanoic acid ChemAxon average_mass 131.1299 ChemAxon mono_mass 131.058243159 ChemAxon smiles N[C@@H](CCC=O)C(O)=O ChemAxon formula C5H9NO3 ChemAxon inchi InChI=1S/C5H9NO3/c6-4(5(8)9)2-1-3-7/h3-4H,1-2,6H2,(H,8,9)/t4-/m0/s1 ChemAxon inchikey KABXUUFDPUOJMW-BYPYZUCNSA-N ChemAxon polar_surface_area 80.39 ChemAxon refractivity 30.36 ChemAxon polarizability 12.56 ChemAxon rotatable_bond_count 4 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Arginine and proline metabolism ec00330 Metabolic pathways eco01100 proline 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. PW000794 Metabolic proline biosynthesis I PROSYN-PWY Specdb::CMs 3271 Specdb::CMs 38271 Specdb::CMs 164942 Specdb::NmrOneD 265528 Specdb::NmrOneD 265529 Specdb::NmrOneD 265530 Specdb::NmrOneD 265531 Specdb::NmrOneD 265532 Specdb::NmrOneD 265533 Specdb::NmrOneD 265534 Specdb::NmrOneD 265535 Specdb::NmrOneD 265536 Specdb::NmrOneD 265537 Specdb::NmrOneD 265538 Specdb::NmrOneD 265539 Specdb::NmrOneD 265540 Specdb::NmrOneD 265541 Specdb::NmrOneD 265542 Specdb::NmrOneD 265543 Specdb::NmrOneD 265544 Specdb::NmrOneD 265545 Specdb::NmrOneD 265546 Specdb::NmrOneD 265547 Specdb::MsMs 27254 Specdb::MsMs 27255 Specdb::MsMs 27256 Specdb::MsMs 33812 Specdb::MsMs 33813 Specdb::MsMs 33814 Specdb::MsMs 2742982 Specdb::MsMs 2742983 Specdb::MsMs 2742984 Specdb::MsMs 2935151 Specdb::MsMs 2935152 Specdb::MsMs 2935153 HMDB02104 193305 167744 C01165 17232 L-GLUTAMATE_GAMMA-SEMIALDEHYDE ILG 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 Gamma-glutamyl phosphate reductase P07004 PROA_ECOLI proA http://ecmdb.ca/proteins/P07004.xml Bifunctional protein putA P09546 PUTA_ECOLI putA http://ecmdb.ca/proteins/P09546.xml Acetylornithine deacetylase P23908 ARGE_ECOLI argE http://ecmdb.ca/proteins/P23908.xml L-Glutamic acid 5-phosphate + Hydrogen ion + NADPH > L-Glutamic-gamma-semialdehyde + NADP + Phosphate GLUTSEMIALDEHYDROG-RXN N-Acetyl-L-glutamate 5-semialdehyde + Water > Acetic acid + L-Glutamic-gamma-semialdehyde L-Glutamic-gamma-semialdehyde > L-D-1-Pyrroline-5-carboxylic acid + Hydrogen ion + Water SPONTPRO-RXN L-Glutamic-gamma-semialdehyde + NAD + Water <> L-Glutamate + NADH + Hydrogen ion R00245 L-Glutamic-gamma-semialdehyde + Phosphate + NADP <> L-Glutamyl 5-phosphate + NADPH + Hydrogen ion + L-Glutamic acid 5-phosphate R03313 Hydrogen ion + L-Glutamate + Adenosine triphosphate + NADPH > ADP + L-Glutamic-gamma-semialdehyde + NADP + Phosphate PROLINE-MULTI L-Glutamic-gamma-semialdehyde <> Hydrogen ion + Water + L-D-1-Pyrroline-5-carboxylic acid SPONTPRO-RXN L-Glutamic-gamma-semialdehyde + Phosphate + NADP < L-Glutamic acid 5-phosphate + NADPH + Hydrogen ion GLUTSEMIALDEHYDROG-RXN L-Glutamic-gamma-semialdehyde + Inorganic phosphate + NADP > L-Glutamic acid 5-phosphate + NADPH L-Glutamic acid 5-phosphate + Hydrogen ion + NADPH + NADPH > L-Glutamic-gamma-semialdehyde + NADP + Phosphate PW_R002716 L-Glutamic-gamma-semialdehyde + NAD + Water >2 Hydrogen ion + NADH + L-Glutamic acid + L-Glutamate PW_R002722 L-Glutamic-gamma-semialdehyde + Phosphate + NADP <> L-Glutamic acid 5-phosphate + NADPH + Hydrogen ion L-Glutamic-gamma-semialdehyde + Phosphate + NADP <> L-Glutamic acid 5-phosphate + NADPH + Hydrogen ion