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MetaCyc Pathway: L-proline degradation
Inferred from experiment

Enzyme View:

Pathway diagram: L-proline degradation

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/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-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

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

L-proline can be catabolized to L-glutamate by the action of two enzymatic activities: EC, proline dehydrogenase (PDH) (sometimes referred to as proline oxidase) and EC, 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 [Lin96b], Agrobacterium tumefaciens [Cho96], 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.

In addition to serving as a building block of proteins, L-proline acts as an osmotic protectant. Consistent with this role, high osmolarity inhibits L-proline degradation.

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

Brandriss79: Brandriss MC, Magasanik B (1979). "Genetics and physiology of proline utilization in Saccharomyces cerevisiae: enzyme induction by proline." J Bacteriol 1979;140(2);498-503. PMID: 387737

Brandriss83: Brandriss MC (1983). "Proline utilization in Saccharomyces cerevisiae: analysis of the cloned PUT2 gene." Mol Cell Biol 1983;3(10);1846-56. PMID: 6358862

Cho96: 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

Lin96b: 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

Menzel81a: Menzel R, Roth J (1981). "Enzymatic properties of the purified putA protein from Salmonella typhimurium." J Biol Chem 256(18);9762-6. PMID: 6270101

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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

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

Bender05: Bender HU, Almashanu S, Steel G, Hu CA, Lin WW, Willis A, Pulver A, Valle D (2005). "Functional consequences of PRODH missense mutations." Am J Hum Genet 76(3);409-20. PMID: 15662599

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

Brown92: Brown ED, Wood JM (1992). "Redesigned purification yields a fully functional PutA protein dimer from Escherichia coli." J Biol Chem 1992;267(18);13086-92. PMID: 1618807

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

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

Commichau08: Commichau FM, Stulke J (2008). "Trigger enzymes: bifunctional proteins active in metabolism and in controlling gene expression." Mol Microbiol 67(4);692-702. PMID: 18086213

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

Editors93: "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.

Forlani97: Forlani, Giuseppe, Scainelli, Damiano, Nielsen, Erik (1997). "Delta1-pyrroline-5-carboxylate dehydrogenase from cultured cells of potato." Plant Physiology 113:1413-1418. PMID: 12223682

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

ForteMcRobbie89: Forte-McRobbie C, Pietruszko R (1989). "Human glutamic-gamma-semialdehyde dehydrogenase. Kinetic mechanism." Biochem J 261(3);935-43. PMID: 2803253

Funck10: Funck D, Eckard S, Muller G (2010). "Non-redundant functions of two proline dehydrogenase isoforms in Arabidopsis." BMC Plant Biol 10;70. PMID: 20403182

Gardan95: Gardan R, Rapoport G, Debarbouille M (1995). "Expression of the rocDEF operon involved in arginine catabolism in Bacillus subtilis." J Mol Biol 1995;249(5);843-56. PMID: 7540694

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

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.5 on Fri Apr 29, 2016, BIOCYC11A.