2.0 2012-05-31 13:49:25 -0600 2015-06-03 15:53:54 -0600 ECMDB01301 M2MDB000329 L-D-1-Pyrroline-5-carboxylic acid (S)-1-Pyrroline-5-carboxylate Pyrroline 5-carboxylate is an enamine or an imino acid that forms on spontaneous dehydration of L-glutamate γ-semialdehyde in aqueous solutions. The stereoisomer (S)-1-Pyrroline-5-carboxylate is an intermediate in glutamate metabolism, in arginine degradation and in proline biosynthesis and degradation and it can be converted to or be formed from the three amino acids L-glutamate, L-ornithine and L-proline. In particular, it is synthesized with the oxidation of proline by pyrroline-5-carboxylate reductase 1 (EC 1.5.1.2, PYCR1) or by proline dehydrogenase (EC 1.5.99.8, PRODH) and it is hydrolyzed to L-glutamate by delta-1-pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12, ALDH4A1). It is also one of the few metabolites that can be a precursor to other metabolites of both the urea cycle and the tricarboxylic acid (TCA) cycle. δ-1-pyrroline-5-carboxylate δ-1-pyrroline-5-carboxylic acid (S)-1-pyrroline-5-carboxylate (S)-1-pyrroline-5-carboxylic acid 1-Pyrroline-5-carboxylate 1-Pyrroline-5-carboxylic acid 3,4-Dihydro-2h-pyrrole-2-carboxylate 3,4-Dihydro-2h-pyrrole-2-carboxylic acid D1-Pyrroline-5-carboxylate D1-Pyrroline-5-carboxylic acid Delta(1)Pyrroline-5-carboxylate Delta(1)Pyrroline-5-carboxylic acid Delta-1-Pyrroline-5-carboxylate Delta-1-Pyrroline-5-carboxylic acid DL-1-Pyrroline-5-carboxylate DL-1-Pyrroline-5-carboxylic acid L-Δ1-pyrroline-5-carboxylate L-Δ1-pyrroline-5-carboxylic acid L-Δ<SUP>1</SUP>-pyrroline-5-carboxylate L-1-Pyrroline-5-carboxylate L-1-Pyrroline-5-carboxylic acid L-D-1-Pyrroline-5-carboxylate L-delta 1-Pyrroline-5-carboxylate L-delta 1-Pyrroline-5-carboxylic acid L-Delta1-pyrroline-5-carboxylate L-Delta1-pyrroline-5-carboxylic acid L-δ 1-Pyrroline-5-carboxylate L-δ 1-Pyrroline-5-carboxylic acid L-δ1-Pyrroline-5-carboxylate L-δ1-Pyrroline-5-carboxylic acid Pyrroline 5-carboxylate Pyrroline 5-carboxylic acid Pyrroline-5-carboxylate Pyrroline-5-carboxylic acid δ(1)Pyrroline-5-carboxylate δ(1)Pyrroline-5-carboxylic acid δ-1-Pyrroline-5-carboxylate δ-1-Pyrroline-5-carboxylic acid C5H7NO2 113.1146 113.047678473 3,4-dihydro-2H-pyrrole-2-carboxylic acid 1-pyrroline-5-carboxylic acid 2906-39-0 OC(=O)C1CCC=N1 InChI=1S/C5H7NO2/c7-5(8)4-2-1-3-6-4/h3-4H,1-2H2,(H,7,8) DWAKNKKXGALPNW-UHFFFAOYSA-N Solid Cytosol logp -0.01 ALOGPS logs -0.94 ALOGPS solubility 1.31e+01 g/l ALOGPS logp -2.3 ChemAxon pka_strongest_acidic 1.82 ChemAxon pka_strongest_basic 6.07 ChemAxon iupac 3,4-dihydro-2H-pyrrole-2-carboxylic acid ChemAxon average_mass 113.1146 ChemAxon mono_mass 113.047678473 ChemAxon smiles OC(=O)C1CCC=N1 ChemAxon formula C5H7NO2 ChemAxon inchi InChI=1S/C5H7NO2/c7-5(8)4-2-1-3-6-4/h3-4H,1-2H2,(H,7,8) ChemAxon inchikey DWAKNKKXGALPNW-UHFFFAOYSA-N ChemAxon polar_surface_area 49.66 ChemAxon refractivity 27.4 ChemAxon polarizability 10.7 ChemAxon rotatable_bond_count 1 ChemAxon acceptor_count 3 ChemAxon donor_count 1 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Alanine, aspartate and glutamate metabolism ec00250 Arginine and proline metabolism ec00330 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 degradation PROUT-PWY proline biosynthesis I PROSYN-PWY Specdb::CMs 2878 Specdb::CMs 38013 Specdb::NmrOneD 319691 Specdb::NmrOneD 319692 Specdb::NmrOneD 319693 Specdb::NmrOneD 319694 Specdb::NmrOneD 319695 Specdb::NmrOneD 319696 Specdb::NmrOneD 319697 Specdb::NmrOneD 319698 Specdb::NmrOneD 319699 Specdb::NmrOneD 319700 Specdb::NmrOneD 319701 Specdb::NmrOneD 319702 Specdb::NmrOneD 319703 Specdb::NmrOneD 319704 Specdb::NmrOneD 319705 Specdb::NmrOneD 319706 Specdb::NmrOneD 319707 Specdb::NmrOneD 319708 Specdb::NmrOneD 319709 Specdb::NmrOneD 319710 Specdb::MsMs 28316 Specdb::MsMs 28317 Specdb::MsMs 28318 Specdb::MsMs 34874 Specdb::MsMs 34875 Specdb::MsMs 34876 Specdb::MsMs 1470821 HMDB01301 1196 1159 C04322 L-DELTA1-PYRROLINE_5-CARBOXYLATE 1-pyrroline-5-carboxylate 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 Simila S: Hydroxyproline metabolism in type II hyperprolinaemia. Ann Clin Biochem. 1979 Jul;16(4):177-81. 533224 Humbertclaude V, Rivier F, Roubertie A, Echenne B, Bellet H, Vallat C, Morin D: Is hyperprolinemia type I actually a benign trait? Report of a case with severe neurologic involvement and vigabatrin intolerance. J Child Neurol. 2001 Aug;16(8):622-3. 11510941 Mixson AJ, Phang JM: The uptake of pyrroline 5-carboxylate. Group translocation mediating the transfer of reducing-oxidizing potential. J Biol Chem. 1988 Aug 5;263(22):10720-4. 3392037 Wakabayashi Y: Tissue-selective expression of enzymes of arginine synthesis. Curr Opin Clin Nutr Metab Care. 1998 Jul;1(4):335-9. 10565370 Onenli-Mungan N, Yuksel B, Elkay M, Topaloglu AK, Baykal T, Ozer G: Type II hyperprolinemia: a case report. Turk J Pediatr. 2004 Apr-Jun;46(2):167-9. 15214748 Fleming GA, Hagedorn CH, Granger AS, Phang JM: Pyrroline-5-carboxylate in human plasma. Metabolism. 1984 Aug;33(8):739-42. 6748947 Vogel, Henry J.; Davis, Bernard D. Glutamic g-semialdehyde and D1-pyrroline-5-carboxylic acid, intermediates in the biosynthesis of proline. Journal of the American Chemical Society (1952), 74 109-12. Bifunctional protein putA P09546 PUTA_ECOLI putA http://ecmdb.ca/proteins/P09546.xml Pyrroline-5-carboxylate reductase P0A9L8 P5CR_ECOLI proC http://ecmdb.ca/proteins/P0A9L8.xml L-D-1-Pyrroline-5-carboxylic acid + 2 Hydrogen ion + NADPH > NADP + L-Proline R01251 FAD + L-Proline > L-D-1-Pyrroline-5-carboxylic acid + FADH2 + Hydrogen ion L-D-1-Pyrroline-5-carboxylic acid + 2 Water + NAD > L-Glutamate + Hydrogen ion + NADH R00707 PYRROLINECARBDEHYDROG-RXN L-Glutamic-gamma-semialdehyde > L-D-1-Pyrroline-5-carboxylic acid + Hydrogen ion + Water SPONTPRO-RXN L-D-1-Pyrroline-5-carboxylic acid + NAD + 2 Water <> L-Glutamate + NADH + Hydrogen ion R00707 L-D-1-Pyrroline-5-carboxylic acid + NADP + 2 Water <> L-Glutamate + NADPH + Hydrogen ion R00708 L-Proline + NAD <> L-D-1-Pyrroline-5-carboxylic acid + NADH + Hydrogen ion R01248 L-Proline + NADP <> L-D-1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen ion R01251 L-Proline + Acceptor + Quinone <> L-D-1-Pyrroline-5-carboxylic acid + Reduced acceptor + (S)-1-pyrroline-5-carboxylate + Hydroquinone R01253 L-Glutamic-gamma-semialdehyde <> Hydrogen ion + Water + L-D-1-Pyrroline-5-carboxylic acid SPONTPRO-RXN L-D-1-Pyrroline-5-carboxylic acid + NAD + Water > Hydrogen ion + L-Glutamate + NADH PYRROLINECARBDEHYDROG-RXN NAD(P)<sup>+</sup> + L-Proline < NAD(P)H + L-D-1-Pyrroline-5-carboxylic acid + Hydrogen ion PYRROLINECARBREDUCT-RXN L-Proline + an oxidized electron acceptor > L-D-1-Pyrroline-5-carboxylic acid + a reduced electron acceptor + Hydrogen ion RXN-821 L-Proline + NAD(P)(+) > L-D-1-Pyrroline-5-carboxylic acid + NAD(P)H 1-Pyrroline-5-carboxylic acid + Hydrogen ion + NADPH + L-D-1-Pyrroline-5-carboxylic acid + NADPH > NADP + L-Proline + L-Proline PW_R002719 L-Proline + Ubiquinone-1 + L-Proline > Hydrogen ion + Ubiquinol-1 + 1-Pyrroline-5-carboxylic acid + L-D-1-Pyrroline-5-carboxylic acid PW_R002720 L-D-1-Pyrroline-5-carboxylic acid + 2 Hydrogen ion + NADPH > NADP + L-Proline L-D-1-Pyrroline-5-carboxylic acid + 2 Water + NAD > L-Glutamate + Hydrogen ion + NADH L-D-1-Pyrroline-5-carboxylic acid + 2 Water + NAD > L-Glutamate + Hydrogen ion + NADH