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Pathway Description
Arginine Metabolism
Escherichia coli
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2015-03-02
Last Updated: 2019-09-03
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
Caldara M, Charlier D, Cunin R: The arginine regulon of Escherichia coli: whole-system transcriptome analysis discovers new genes and provides an integrated view of arginine regulation. Microbiology. 2006 Nov;152(Pt 11):3343-54. doi: 10.1099/mic.0.29088-0.
Pubmed: 17074904
MAAS WK: STUDIES ON THE MECHANISM OF REPRESSION OF ARGININE BIOSYNTHESIS IN ESCHERICHIA COLI. II. DOMINANCE OF REPRESSIBILITY IN DIPLOIDS. J Mol Biol. 1964 Mar;8:365-70.
Pubmed: 14168690
Weerasinghe JP, Dong T, Schertzberg MR, Kirchhof MG, Sun Y, Schellhorn HE: Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli. BMC Microbiol. 2006 Feb 22;6:14. doi: 10.1186/1471-2180-6-14.
Pubmed: 16504055
Caldovic L, Tuchman M: N-acetylglutamate and its changing role through evolution. Biochem J. 2003 Jun 1;372(Pt 2):279-90. doi: 10.1042/BJ20030002.
Pubmed: 12633501
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.
Pubmed: 2851495
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.
Pubmed: 8265357
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
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.
Pubmed: 16738553
Van Vliet F, Cunin R, Jacobs A, Piette J, Gigot D, Lauwereys M, Pierard A, Glansdorff N: Evolutionary divergence of genes for ornithine and aspartate carbamoyl-transferases--complete sequence and mode of regulation of the Escherichia coli argF gene; comparison of argF with argI and pyrB. Nucleic Acids Res. 1984 Aug 10;12(15):6277-89. doi: 10.1093/nar/12.15.6277.
Pubmed: 6382166
Bencini DA, Houghton JE, Hoover TA, Foltermann KF, Wild JR, O'Donovan GA: The DNA sequence of argI from Escherichia coli K12. Nucleic Acids Res. 1983 Dec 10;11(23):8509-18. doi: 10.1093/nar/11.23.8509.
Pubmed: 6369246
Legrain C, Stalon V, Glansdorff N: Escherichia coli ornithine carbamolytransferase isoenzymes: evolutionary significance and the isolation of lambdaargF and lambdaargI transducing bacteriophages. J Bacteriol. 1976 Oct;128(1):35-8.
Pubmed: 789338
Kuo LC, Miller AW, Lee S, Kozuma C: Site-directed mutagenesis of Escherichia coli ornithine transcarbamoylase: role of arginine-57 in substrate binding and catalysis. Biochemistry. 1988 Nov 29;27(24):8823-32. doi: 10.1021/bi00424a021.
Pubmed: 3072022
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
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