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Pathway Description
Arginine Metabolism
Escherichia coli SE15
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2025-02-20
Last Updated: 2025-08-23
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
Parsot C, Boyen A, Cohen GN, Glansdorff N: Nucleotide sequence of Escherichia coli argB and argC genes: comparison of N-acetylglutamate kinase and N-acetylglutamate-gamma-semialdehyde dehydrogenase with homologous and analogous enzymes. Gene. 1988 Sep 7;68(2):275-83. doi: 10.1016/0378-1119(88)90030-3.
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Blattner FR, Burland V, Plunkett G 3rd, Sofia HJ, Daniels DL: Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes. Nucleic Acids Res. 1993 Nov 25;21(23):5408-17. doi: 10.1093/nar/21.23.5408.
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Heimberg H, Boyen A, Crabeel M, Glansdorff N: Escherichia coli and Saccharomyces cerevisiae acetylornithine aminotransferase: evolutionary relationship with ornithine aminotransferase. Gene. 1990 May 31;90(1):69-78. doi: 10.1016/0378-1119(90)90440-3.
Pubmed: 2199330
Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. doi: 10.1038/msb4100049. Epub 2006 Feb 21.
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Nyunoya H, Lusty CJ: The carB gene of Escherichia coli: a duplicated gene coding for the large subunit of carbamoyl-phosphate synthetase. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4629-33. doi: 10.1073/pnas.80.15.4629.
Pubmed: 6308632
Bouvier J, Patte JC, Stragier P: Multiple regulatory signals in the control region of the Escherichia coli carAB operon. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4139-43. doi: 10.1073/pnas.81.13.4139.
Pubmed: 6377309
Yura T, Mori H, Nagai H, Nagata T, Ishihama A, Fujita N, Isono K, Mizobuchi K, Nakata A: Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region. Nucleic Acids Res. 1992 Jul 11;20(13):3305-8. doi: 10.1093/nar/20.13.3305.
Pubmed: 1630901
Piette J, Nyunoya H, Lusty CJ, Cunin R, Weyens G, Crabeel M, Charlier D, Glansdorff N, Pierard A: DNA sequence of the carA gene and the control region of carAB: tandem promoters, respectively controlled by arginine and the pyrimidines, regulate the synthesis of carbamoyl-phosphate synthetase in Escherichia coli K-12. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4134-8. doi: 10.1073/pnas.81.13.4134.
Pubmed: 6330744
Van Vliet F, Crabeel M, Boyen A, Tricot C, Stalon V, Falmagne P, Nakamura Y, Baumberg S, Glansdorff N: Sequences of the genes encoding argininosuccinate synthetase in Escherichia coli and Saccharomyces cerevisiae: comparison with methanogenic archaebacteria and mammals. Gene. 1990 Oct 30;95(1):99-104. doi: 10.1016/0378-1119(90)90419-r.
Pubmed: 2123815
Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kasai H, Kashimoto K, Kimura S, Kitakawa M, Kitagawa M, Makino K, Miki T, Mizobuchi K, Mori H, Mori T, Motomura K, Nakade S, Nakamura Y, Nashimoto H, Nishio Y, Oshima T, Saito N, Sampei G, Horiuchi T, et al.: A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map. DNA Res. 1996 Dec 31;3(6):363-77. doi: 10.1093/dnares/3.6.363.
Pubmed: 9097039
Kurihara S, Oda S, Kato K, Kim HG, Koyanagi T, Kumagai H, Suzuki H: A novel putrescine utilization pathway involves gamma-glutamylated intermediates of Escherichia coli K-12. J Biol Chem. 2005 Feb 11;280(6):4602-8. doi: 10.1074/jbc.M411114200. Epub 2004 Dec 8.
Pubmed: 15590624
Heim R, Strehler EE: Cloning an Escherichia coli gene encoding a protein remarkably similar to mammalian aldehyde dehydrogenases. Gene. 1991 Mar 1;99(1):15-23. doi: 10.1016/0378-1119(91)90028-a.
Pubmed: 1840553
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
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