Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Arginine Metabolism
Pseudomonas aeruginosa
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2019-08-12
Last Updated: 2019-09-15
The metabolism of L-arginine starts with the acetylation of L-glutamic acid resulting in a N-acetylglutamic acid while releasing a coenzyme A and a hydrogen ion. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. This compound undergoes a NDPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde, which then reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce an N-acetylornithine. Next N-acetylornithine is deacetylated through a acetylornithine deacetylase yielding an ornithine.
L-glutamine is used to synthesize carbamoyl phosphate through the interaction of L-glutamine, water, ATP, and hydrogen carbonate. This reaction yields ADP, L-glutamic acid, phosphate, and hydrogen ion.
Carbamoyl phosphate and ornithine are used to catalyze the production of citrulline through an ornithine carbamoyltransferase. Citrulline reacts with L-aspartic acid through an ATP dependent enzyme, argininosuccinate synthase to produce pyrophosphate, AMP and argininosuccinic acid. Argininosussinic acid is then lyase to produce L-arginine and fumaric acid.
L-arginine can be metabolized into succinic acid by two different sets of reactions:
1. Arginine reacts with succinyl-CoA through a arginine N-succinyltransferase resulting in N2-succinyl-L-arginine while releasing CoA and Hydrogen Ion. N2-succinyl-L-arginine is then dihydrolase to produce a N2-succinyl-L-ornithine through a N-succinylarginine dihydrolase which in turn reacts with oxoglutaric acid through succinylornithine transaminase resulting in L-glutamic acid and N2-succinyl-L-glutamic acid 5-semialdehyde. Next N2-succinyl-L-glutamic acid 5-semialdehyde reacts with a NAD dependent dehydrogenase resulting in N2-succinylglutamate and releases NADH and hydrogen ion. Finally, N2-succinylglutamate reacts with water through a succinylglutamate desuccinylase resulting in L-glutamic acid and a succinic acid. The succinic acid is then incorporated in the TCA cycle
2. Argine reacts with carbon dioxide and a hydrogen ion through a biodegradative arginine decarboxylase, resulting in Agmatine. Agmatine is transformed into putrescine by reacting with water and an agmatinase, and releasing urea. Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. Gamma-glutamyl-L-putrescine is reduced via interactions with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. Dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase, 4-gamma-glutamylamino butanal is converted into hydrogen ions, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde, which continues and reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid. Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. Succinic acid semialdehyde then reacts with either NADP or NAD to produce succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle.
References
Arginine Metabolism References
Itoh Y: Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J Bacteriol. 1997 Dec;179(23):7280-90. doi: 10.1128/jb.179.23.7280-7290.1997.
Pubmed: 9393691
Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000 Aug 31;406(6799):959-64. doi: 10.1038/35023079.
Pubmed: 10984043
Park SM, Lu CD, Abdelal AT: Cloning and characterization of argR, a gene that participates in regulation of arginine biosynthesis and catabolism in Pseudomonas aeruginosa PAO1. J Bacteriol. 1997 Sep;179(17):5300-8. doi: 10.1128/jb.179.17.5300-5308.1997.
Pubmed: 9286980
Lu CD, Kwon DH, Abdelal AT: Identification of greA encoding a transcriptional elongation factor as a member of the carA-orf-carB-greA operon in Pseudomonas aeruginosa PAO1. J Bacteriol. 1997 May;179(9):3043-6. doi: 10.1128/jb.179.9.3043-3046.1997.
Pubmed: 9139926
Kwon DH, Lu CD, Walthall DA, Brown TM, Houghton JE, Abdelal AT: Structure and regulation of the carAB operon in Pseudomonas aeruginosa and Pseudomonas stutzeri: no untranslated region exists. J Bacteriol. 1994 May;176(9):2532-42. doi: 10.1128/jb.176.9.2532-2542.1994.
Pubmed: 8169201
Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S, Diggins LT, He J, Saucier M, Deziel E, Friedman L, Li L, Grills G, Montgomery K, Kucherlapati R, Rahme LG, Ausubel FM: Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol. 2006;7(10):R90. doi: 10.1186/gb-2006-7-10-r90. Epub 2006 Oct 12.
Pubmed: 17038190
Tricot C, Vander Wauven C, Wattiez R, Falmagne P, Stalon V: Purification and properties of a succinyltransferase from Pseudomonas aeruginosa specific for both arginine and ornithine. Eur J Biochem. 1994 Sep 15;224(3):853-61. doi: 10.1111/j.1432-1033.1994.00853.x.
Pubmed: 7523119
Yamanishi Y, Mihara H, Osaki M, Muramatsu H, Esaki N, Sato T, Hizukuri Y, Goto S, Kanehisa M: Prediction of missing enzyme genes in a bacterial metabolic network. Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa. FEBS J. 2007 May;274(9):2262-73. doi: 10.1111/j.1742-4658.2007.05763.x. Epub 2007 Mar 27.
Pubmed: 17388807
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000812
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings