This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: L-proline utilization
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-proline Degradation|
Some taxa known to possess this pathway include : Agrobacterium tumefaciens , Arabidopsis thaliana col , Bradyrhizobium japonicum , Escherichia coli K-12 substr. MG1655 , Homo sapiens , Photobacterium leiognathi leiognathi , Rhodobacter capsulatus , Saccharomyces cerevisiae , Salmonella enterica enterica serovar Typhimurium , Sinorhizobium meliloti Rm2011 , Solanum tuberosum
L-proline can be catabolized to L-glutamate by the action of two enzymatic activities: EC 220.127.116.11, proline dehydrogenase (PDH) (sometimes referred to as proline oxidase) and EC 18.104.22.168, L-glutamate γ-semialdehyde dehydrogenase (previously known as Δ-pyrroline-5-carboxylate dehydrogenase, or P5CDH).
Whereas in eukaryotes PDH and P5CDH are encoded by two different genes, in most bacteria, including enteric bacteria [Menzel81, Menzel81a], Rhodobacter capsulatus [Keuntje95], Bradyrhizobium japonicum [Straub96], Photobacterium leiognathi leiognathi [Lin96a], Agrobacterium tumefaciens [Cho96a], and Sinorhizobium meliloti Rm2011 [Soto00], both steps are catalyzed by a single polypeptide encoded by the putA gene. The enzyme is highly conserved among different microorganisms, but its genetic organization and control of expression are highly divergent [Soto00].
Saccharomyces cerevisiae is able to utilize proline as a sole nitrogen source. L-proline is catabolized within the mitochondrial matrix. Since both enzymes are encoded in the nucleus and synthesized in the cytoplasm, they are imported into the mitochondria before they become active [Brandriss79, Brandriss83].
L-proline can serve as a total source of carbon and energy or of nitrogen for Escherichia coli. In the two steps (both of which are catalyzed by a product of putA) shown here, proline is converted to L-glutamate, which is further degraded to 2-oxoglutarate, an intermediate of the TCA cycle I (prokaryotic). Curiously, L-glutamate, the product of L-proline degradation, cannot itself serve as a total source of carbon and energy for Escherichia coli because L-glutamate transport supplies exogenous L-glutamate at an inadequate rate.
The pathway is shown here in three steps because L-glutamate-5-semialdehyde is an intermediate between (S)-1-pyrroline-5-carboxylate and L-glutamate. The hydrolysis of (S)-1-pyrroline-5-carboxylate to L-glutamate-5-semialdehyde occurs spontaneously.
Created 22-May-1996 by Riley M , Marine Biological Laboratory
Revised 30-Sep-2005 by Caspi R , SRI International
Revised 14-Jul-2006 by Ingraham JL , UC Davis
Revised 17-Apr-2013 by Caspi R , SRI International
Abrahamson83: Abrahamson JL, Baker LG, Stephenson JT, Wood JM (1983). "Proline dehydrogenase from Escherichia coli K12. Properties of the membrane-associated enzyme." Eur J Biochem 1983;134(1);77-82. PMID: 6305659
Cho96a: Cho K, Winans SC (1996). "The putA gene of Agrobacterium tumefaciens is transcriptionally activated in response to proline by an Lrp-like protein and is not autoregulated." Mol Microbiol 22(5);1025-33. PMID: 8971722
Keuntje95: Keuntje B, Masepohl B, Klipp W (1995). "Expression of the putA gene encoding proline dehydrogenase from Rhodobacter capsulatus is independent of NtrC regulation but requires an Lrp-like activator protein." J Bacteriol 177(22);6432-9. PMID: 7592417
Lin96a: Lin JW, Yu KY, Chen HY, Weng SF (1996). "Regulatory region with putA gene of proline dehydrogenase that links to the lum and the lux operons in Photobacterium leiognathi." Biochem Biophys Res Commun 219(3);868-75. PMID: 8645272
Menzel81: Menzel R, Roth J (1981). "Purification of the putA gene product. A bifunctional membrane-bound protein from Salmonella typhimurium responsible for the two-step oxidation of proline to glutamate." J Biol Chem 256(18);9755-61. PMID: 6270100
Soto00: Soto MJ, Jimenez-Zurdo JI, van Dillewijn P, Toro N (2000). "Sinorhizobium meliloti putA gene regulation: a new model within the family Rhizobiaceae." J Bacteriol 182(7);1935-41. PMID: 10715000
Straub96: Straub PF, Reynolds PH, Althomsons S, Mett V, Zhu Y, Shearer G, Kohl DH (1996). "Isolation, DNA sequence analysis, and mutagenesis of a proline dehydrogenase gene (putA) from Bradyrhizobium japonicum." Appl Environ Microbiol 62(1);221-9. PMID: 8572700
Baban04: Baban BA, Vinod MP, Tanner JJ, Becker DF (2004). "Probing a hydrogen bond pair and the FAD redox properties in the proline dehydrogenase domain of Escherichia coli PutA." Biochim Biophys Acta 1701(1-2);49-59. PMID: 15450175
Becker01a: Becker DF, Thomas EA (2001). "Redox properties of the PutA protein from Escherichia coli and the influence of the flavin redox state on PutA-DNA interactions." Biochemistry 40(15);4714-21. PMID: 11294639
Brandriss81: Brandriss MC, Magasanik B (1981). "Subcellular compartmentation in control of converging pathways for proline and arginine metabolism in Saccharomyces cerevisiae." J Bacteriol 145(3);1359-64. PMID: 7009582
Brown93: Brown ED, Wood JM (1993). "Conformational change and membrane association of the PutA protein are coincident with reduction of its FAD cofactor by proline." J Biol Chem 1993;268(12);8972-9. PMID: 8473341
BSUB93: "Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics." (1993). Editors: Sonenshein, A.L., Hoch, J.A., Losick, R. American Society For Microbiology, Washington, DC.
Campbell97: Campbell HD, Webb GC, Young IG (1997). "A human homologue of the Drosophila melanogaster sluggish-A (proline oxidase) gene maps to 22q11.2, and is a candidate gene for type-I hyperprolinaemia." Hum Genet 101(1);69-74. PMID: 9385373
Deuschle01: Deuschle K, Funck D, Hellmann H, Daschner K, Binder S, Frommer WB (2001). "A nuclear gene encoding mitochondrial Delta-pyrroline-5-carboxylate dehydrogenase and its potential role in protection from proline toxicity." Plant J 27(4);345-56. PMID: 11532180
Deuschle04: Deuschle K, Funck D, Forlani G, Stransky H, Biehl A, Leister D, van der Graaff E, Kunze R, Frommer WB (2004). "The role of [Delta]1-pyrroline-5-carboxylate dehydrogenase in proline degradation." Plant Cell 16(12);3413-25. PMID: 15548746
Deutch89: Deutch CE, Hasler JM, Houston RM, Sharma M, Stone VJ (1989). "Nonspecific inhibition of proline dehydrogenase synthesis in Escherichia coli during osmotic stress." Can J Microbiol 35(8);779-85. PMID: 2684374
Donald01: Donald SP, Sun XY, Hu CA, Yu J, Mei JM, Valle D, Phang JM (2001). "Proline oxidase, encoded by p53-induced gene-6, catalyzes the generation of proline-dependent reactive oxygen species." Cancer Res 61(5);1810-5. PMID: 11280728
ForteMcRobbie86: Forte-McRobbie CM, Pietruszko R (1986). "Purification and characterization of human liver "high Km" aldehyde dehydrogenase and its identification as glutamic gamma-semialdehyde dehydrogenase." J Biol Chem 261(5);2154-63. PMID: 3944130
Gardan97: Gardan R, Rapoport G, Debarbouille M (1997). "Role of the transcriptional activator RocR in the arginine-degradation pathway of Bacillus subtilis." Mol Microbiol 1997;24(4);825-37. PMID: 9194709
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