2.02012-05-31 13:49:25 -06002015-06-03 15:53:54 -0600ECMDB01301M2MDB000329L-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-carboxylateδ-1-pyrroline-5-carboxylic acid(S)-1-pyrroline-5-carboxylate(S)-1-pyrroline-5-carboxylic acid1-Pyrroline-5-carboxylate1-Pyrroline-5-carboxylic acid3,4-Dihydro-2h-pyrrole-2-carboxylate3,4-Dihydro-2h-pyrrole-2-carboxylic acidD1-Pyrroline-5-carboxylateD1-Pyrroline-5-carboxylic acidDelta(1)Pyrroline-5-carboxylateDelta(1)Pyrroline-5-carboxylic acidDelta-1-Pyrroline-5-carboxylateDelta-1-Pyrroline-5-carboxylic acidDL-1-Pyrroline-5-carboxylateDL-1-Pyrroline-5-carboxylic acidL-Δ1-pyrroline-5-carboxylateL-Δ1-pyrroline-5-carboxylic acidL-Δ<SUP>1</SUP>-pyrroline-5-carboxylateL-1-Pyrroline-5-carboxylateL-1-Pyrroline-5-carboxylic acidL-D-1-Pyrroline-5-carboxylateL-delta 1-Pyrroline-5-carboxylateL-delta 1-Pyrroline-5-carboxylic acidL-Delta1-pyrroline-5-carboxylateL-Delta1-pyrroline-5-carboxylic acidL-δ 1-Pyrroline-5-carboxylateL-δ 1-Pyrroline-5-carboxylic acidL-δ1-Pyrroline-5-carboxylateL-δ1-Pyrroline-5-carboxylic acidPyrroline 5-carboxylatePyrroline 5-carboxylic acidPyrroline-5-carboxylatePyrroline-5-carboxylic acidδ(1)Pyrroline-5-carboxylateδ(1)Pyrroline-5-carboxylic acidδ-1-Pyrroline-5-carboxylateδ-1-Pyrroline-5-carboxylic acidC5H7NO2113.1146113.0476784733,4-dihydro-2H-pyrrole-2-carboxylic acid1-pyrroline-5-carboxylic acid2906-39-0OC(=O)C1CCC=N1InChI=1S/C5H7NO2/c7-5(8)4-2-1-3-6-4/h3-4H,1-2H2,(H,7,8)DWAKNKKXGALPNW-UHFFFAOYSA-NSolidCytosollogp-0.01logs-0.94solubility1.31e+01 g/llogp-2.3pka_strongest_acidic1.82pka_strongest_basic6.07iupac3,4-dihydro-2H-pyrrole-2-carboxylic acidaverage_mass113.1146mono_mass113.047678473smilesOC(=O)C1CCC=N1formulaC5H7NO2inchiInChI=1S/C5H7NO2/c7-5(8)4-2-1-3-6-4/h3-4H,1-2H2,(H,7,8)inchikeyDWAKNKKXGALPNW-UHFFFAOYSA-Npolar_surface_area49.66refractivity27.4polarizability10.7rotatable_bond_count1acceptor_count3donor_count1physiological_charge-1formal_charge0Alanine, aspartate and glutamate metabolismec00250Arginine and proline metabolismec00330proline 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 degradationPROUT-PWYproline biosynthesis IPROSYN-PWYSpecdb::CMs2878Specdb::CMs38013Specdb::NmrOneD319691Specdb::NmrOneD319692Specdb::NmrOneD319693Specdb::NmrOneD319694Specdb::NmrOneD319695Specdb::NmrOneD319696Specdb::NmrOneD319697Specdb::NmrOneD319698Specdb::NmrOneD319699Specdb::NmrOneD319700Specdb::NmrOneD319701Specdb::NmrOneD319702Specdb::NmrOneD319703Specdb::NmrOneD319704Specdb::NmrOneD319705Specdb::NmrOneD319706Specdb::NmrOneD319707Specdb::NmrOneD319708Specdb::NmrOneD319709Specdb::NmrOneD319710Specdb::MsMs28316Specdb::MsMs28317Specdb::MsMs28318Specdb::MsMs34874Specdb::MsMs34875Specdb::MsMs34876Specdb::MsMs1470821HMDB0130111961159C04322L-DELTA1-PYRROLINE_5-CARBOXYLATE1-pyrroline-5-carboxylateKeseler, 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-D114.22080510Simila S: Hydroxyproline metabolism in type II hyperprolinaemia. Ann Clin Biochem. 1979 Jul;16(4):177-81.533224Humbertclaude 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):622-3.11510941Mixson 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):10720-4.3392037Wakabayashi Y: Tissue-selective expression of enzymes of arginine synthesis. Curr Opin Clin Nutr Metab Care. 1998 Jul;1(4):335-9.10565370Onenli-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):167-9.15214748Fleming GA, Hagedorn CH, Granger AS, Phang JM: Pyrroline-5-carboxylate in human plasma. Metabolism. 1984 Aug;33(8):739-42.6748947Vogel, 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 putAP09546PUTA_ECOLIputAhttp://ecmdb.ca/proteins/P09546.xmlPyrroline-5-carboxylate reductaseP0A9L8P5CR_ECOLIproChttp://ecmdb.ca/proteins/P0A9L8.xmlL-D-1-Pyrroline-5-carboxylic acid + 2 Hydrogen ion + NADPH > NADP + L-ProlineR01251FAD + L-Proline > L-D-1-Pyrroline-5-carboxylic acid + FADH2 + Hydrogen ionL-D-1-Pyrroline-5-carboxylic acid + 2 Water + NAD > L-Glutamate + Hydrogen ion + NADHR00707PYRROLINECARBDEHYDROG-RXNL-Glutamic-gamma-semialdehyde > L-D-1-Pyrroline-5-carboxylic acid + Hydrogen ion + WaterSPONTPRO-RXNL-D-1-Pyrroline-5-carboxylic acid + NAD + 2 Water <> L-Glutamate + NADH + Hydrogen ionR00707L-D-1-Pyrroline-5-carboxylic acid + NADP + 2 Water <> L-Glutamate + NADPH + Hydrogen ionR00708L-Proline + NAD <> L-D-1-Pyrroline-5-carboxylic acid + NADH + Hydrogen ionR01248L-Proline + NADP <> L-D-1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen ionR01251L-Proline + Acceptor + Quinone <> L-D-1-Pyrroline-5-carboxylic acid + Reduced acceptor + (S)-1-pyrroline-5-carboxylate + HydroquinoneR01253L-Glutamic-gamma-semialdehyde <> Hydrogen ion + Water + L-D-1-Pyrroline-5-carboxylic acidSPONTPRO-RXNL-D-1-Pyrroline-5-carboxylic acid + NAD + Water > Hydrogen ion + L-Glutamate + NADHPYRROLINECARBDEHYDROG-RXNNAD(P)<sup>+</sup> + L-Proline < NAD(P)H + L-D-1-Pyrroline-5-carboxylic acid + Hydrogen ionPYRROLINECARBREDUCT-RXNL-Proline + an oxidized electron acceptor > L-D-1-Pyrroline-5-carboxylic acid + a reduced electron acceptor + Hydrogen ionRXN-821L-Proline + NAD(P)(+) > L-D-1-Pyrroline-5-carboxylic acid + NAD(P)H1-Pyrroline-5-carboxylic acid + Hydrogen ion + NADPH + L-D-1-Pyrroline-5-carboxylic acid + NADPH > NADP + L-Proline + L-ProlinePW_R002719L-Proline + Ubiquinone-1 + L-Proline > Hydrogen ion + Ubiquinol-1 + 1-Pyrroline-5-carboxylic acid + L-D-1-Pyrroline-5-carboxylic acidPW_R002720L-D-1-Pyrroline-5-carboxylic acid + 2 Hydrogen ion + NADPH > NADP + L-ProlineL-D-1-Pyrroline-5-carboxylic acid + 2 Water + NAD > L-Glutamate + Hydrogen ion + NADHL-D-1-Pyrroline-5-carboxylic acid + 2 Water + NAD > L-Glutamate + Hydrogen ion + NADH