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MetaCyc Pathway: L-arginine biosynthesis I (via L-ornithine)
Traceable author statement to experimental support

Pathway diagram: L-arginine biosynthesis I (via L-ornithine)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-arginine Biosynthesis

Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655, Moritella sp., Myxococcus xanthus, Salmonella enterica enterica serovar Typhimurium, Vibrionaceae

Expected Taxonomic Range: Archaea, Bacteria , Viridiplantae

General Background

Arginine biosynthesis is notable for its complexity and variability at the genetic level, and by its connection with several other pathways, such as pyrimidine and polyamine biosynthesis, and certain degradative pathways. The initial steps of the arginine biosynthetic pathways proceed via N-acetylated intermediates. The presumed reason for this is that the acetylation prevents the spontaneous cyclization of glutamate derivatives, which leads to proline biosynthesis, thus keeping the two pathways separate [Caldovic03]. A variation of the pathway found in some archaebacteria and hyperthermophilic bacteria utilizes a dedicated carrier protein to protect the intermediates instead of acetylation.

Several alternative arginine biosynthetic pathways have evolved in bacteria:

In L-arginine biosynthesis I (via L-ornithine), which is not very common, the key intermediate N-acetyl-L-glutamate (NAG) is formed by the enzyme EC, amino-acid N-acetyltransferase. A second key intermediate downstream, N-acetyl-L-ornithine, is hydrolyzed by the enzyme EC, acetylornithine deacetylase, releasing acetate, and forming the arginine precursor L-ornithine.

In L-arginine biosynthesis II (acetyl cycle)), which is found in most of the prokaryotic and eukaryotic microbes investigated up to now, the two reactions mentioned above are linked: the acetyl group which is removed from N-acetyl-L-ornithine is recycled onto glutamate, regenerating N-acetyl-L-glutamate (NAG). This recycling is performed by the enzyme EC, glutamate N-acetyltransferase. This pathway is considered more evolved, since the overall reaction is energetically more favorable [Cunin86].

The variant L-arginine biosynthesis III (via N-acetyl-L-citrulline) is found in several eubacteria. While in the two pathways mentioned above N-acetyl-L-ornithine is deacetylate to L-ornithine, which is subsequntly transcarbamoylated to form L-citrulline, in this variant N-acetyl-L-ornithine is not deacetylated. Instead, it is transcarbamoylated directly by the enzyme EC, N-acetylornithine carbamoyltransferase, resulting in N-acetyl-L-citrulline. The enzyme acetylornithine deacetylase can accept N-acetyl-L-citrulline as a substrate, and deacetylates it into L-citrulline [Morizono06].

The variant L-arginine biosynthesis IV (archaebacteria), which has been described in the archaebacterium Sulfolobus acidocaldarius, involves early intermediates that are protected not by acetylation but by a carrier protein (the LysW [LysW L-2-aminoadipate carrier protein]), which participates in the biosynthesis of both L-arginine and L-leucine in these organsims [Ouchi13].

About This Pathway

This linear variant of the arginine biosynthesis pathway has been reported from the Enterobacteriaceae [Cunin86], the Vibrionaceae [Xu00], and the Gram-negative bacterium Myxococcus xanthus [Harris98]. The pathway was also described in the archaeon Sulfolobus solfataricus [VandeCasteele90], but in most likelihood that organism possesses a different variant of the pathway (see L-arginine biosynthesis IV (archaebacteria)).

In this pathway glutamate is acetylated to N-acetyl-glutamate (NAG) by the enzyme NAG synthase, encoded by the argA gene. The acetyl donor for this reaction is acetyl-CoA. NAG is then converted in several enzymatic steps to N-acetyl-ornithine. The acetyl group is removed in the form of acetate by the enzyme acetylornithine deacetylase, encoded by the argE gene. Ornithine is then combined with carbamoyl phosphate to form citrulline, which is converted in two steps to L-arginine.

Superpathways: superpathway of arginine and polyamine biosynthesis

Subpathways: L-ornithine biosynthesis I

Variants: L-arginine biosynthesis II (acetyl cycle), L-arginine biosynthesis III (via N-acetyl-L-citrulline), L-arginine biosynthesis IV (archaebacteria), L-citrulline-nitric oxide cycle

Unification Links: EcoCyc:ARGSYN-PWY

Created 02-Feb-1994 by Riley M, Marine Biological Laboratory
Revised 14-Apr-2006 by Caspi R, SRI International
Last-Curated 30-Mar-2011 by Fulcher CA, SRI International


Caldovic03: Caldovic L, Tuchman M (2003). "N-acetylglutamate and its changing role through evolution." Biochem J 372(Pt 2);279-90. PMID: 12633501

Cunin86: Cunin R, Glansdorff N, Pierard A, Stalon V (1986). "Biosynthesis and metabolism of arginine in bacteria." Microbiol Rev 1986;50(3);314-52. PMID: 3534538

Harris98: Harris BZ, Singer M (1998). "Identification and characterization of the Myxococcus xanthus argE gene." J Bacteriol 180(23);6412-4. PMID: 9829957

Morizono06: Morizono H, Cabrera-Luque J, Shi D, Gallegos R, Yamaguchi S, Yu X, Allewell NM, Malamy MH, Tuchman M (2006). "Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis." J Bacteriol 188(8);2974-82. PMID: 16585758

Ouchi13: Ouchi T, Tomita T, Horie A, Yoshida A, Takahashi K, Nishida H, Lassak K, Taka H, Mineki R, Fujimura T, Kosono S, Nishiyama C, Masui R, Kuramitsu S, Albers SV, Kuzuyama T, Nishiyama M (2013). "Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus." Nat Chem Biol 9(4);277-83. PMID: 23434852

VandeCasteele90: Van-de-Casteele, M., Demarez, M., Lagrain, C., Glansdorff, N., Pierard, A. (1990). "Pathways of arginine biosynthesis in extreme thermophilic archaeo- and eubacteria." J. Gen. Microbiol. 136:1177-1183.

Xu00: Xu Y, Liang Z, Legrain C, Ruger HJ, Glansdorff N (2000). "Evolution of arginine biosynthesis in the bacterial domain: novel gene-enzyme relationships from psychrophilic Moritella strains (Vibrionaceae) and evolutionary significance of N-alpha-acetyl ornithinase." J Bacteriol 182(6);1609-15. PMID: 10692366

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

Anderson75: Anderson PM, Carlson JD (1975). "Reversible reaction of cyanate with a reactive sulfhydryl group at the glutamine binding site of carbamyl phosphate synthetase." Biochemistry 1975;14(16);3688-94. PMID: 240389

Anderson77: Anderson PM (1977). "Binding of allosteric effectors to carbamyl-phosphate synthetase from Escherichia coli." Biochemistry 1977;16(4);587-93. PMID: 189806

BacaDeLancey99: Baca-DeLancey RR, South MM, Ding X, Rather PN (1999). "Escherichia coli genes regulated by cell-to-cell signaling." Proc Natl Acad Sci U S A 96(8);4610-4. PMID: 10200310

Baich62: Baich A, Vogel HJ (1962). "N-Acetyl-gamma-Ilutamokinase and N-acetylglutamic gamma-semialdehyde dehydrogenase: repressible enzymes of arginine synthesis in Escherichia coli." Biochem Biophys Res Commun 7;491-6. PMID: 13863980

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Bartsch90: Bartsch K, von Johnn-Marteville A, Schulz A (1990). "Molecular analysis of two genes of the Escherichia coli gab cluster: nucleotide sequence of the glutamate:succinic semialdehyde transaminase gene (gabT) and characterization of the succinic semialdehyde dehydrogenase gene (gabD)." J Bacteriol 1990;172(12);7035-42. PMID: 2254272

Baur90: Baur H, Tricot C, Stalon V, Haas D (1990). "Converting catabolic ornithine carbamoyltransferase to an anabolic enzyme." J Biol Chem 265(25);14728-31. PMID: 2118516

Becker01: Becker G, Hengge-Aronis R (2001). "What makes an Escherichia coli promoter sigma(S) dependent? Role of the -13/-14 nucleotide promoter positions and region 2.5 of sigma(S)." Mol Microbiol 39(5);1153-65. PMID: 11251833

Berg74: Berg CM, Rossi JJ (1974). "Proline excretion and indirect suppression in Escherichia coli and Salmonella typhimurium." J Bacteriol 118(3);928-34. PMID: 4598010

Bhaumik04: Bhaumik P, Koski MK, Bergmann U, Wierenga RK (2004). "Structure determination and refinement at 2.44 A resolution of argininosuccinate lyase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 60(Pt 11);1964-70. PMID: 15502303

Billheimer79: Billheimer JT, Shen MY, Carnevale HN, Horton HR, Jones EE (1979). "Isolation and characterization of acetylornithine delta-transaminase of wild-type Escherichia coli W. Comparison with arginine-inducible acetylornithine delta-transaminase." Arch Biochem Biophys 1979;195(2);401-13. PMID: 112925

Billhemier76: Billhemier JT, Carnevale HN, Leisinger T, Eckhardt T, Jones EE (1976). "Ornithine delta-transaminase activity in Escherichia coli: its identity with acetylornithine delta-transaminase." J Bacteriol 127(3);1315-23. PMID: 8431

Boyen92: Boyen A, Charlier D, Charlier J, Sakanyan V, Mett I, Glansdorff N (1992). "Acetylornithine deacetylase, succinyldiaminopimelate desuccinylase and carboxypeptidase G2 are evolutionarily related." Gene 1992;116(1);1-6. PMID: 1628835

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Brown87: Brown K, Finch PW, Hickson ID, Emmerson PT (1987). "Complete nucleotide sequence of the Escherichia coli argA gene." Nucleic Acids Res 1987;15(24);10586. PMID: 3320971

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.

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Chen05a: Chen L, Brugger K, Skovgaard M, Redder P, She Q, Torarinsson E, Greve B, Awayez M, Zibat A, Klenk HP, Garrett RA (2005). "The genome of Sulfolobus acidocaldarius, a model organism of the Crenarchaeota." J Bacteriol 187(14);4992-9. PMID: 15995215

Coleman77: Coleman PF, Suttle DP, Stark GR (1977). "Purification from hamster cells of the multifunctional protein that initiates de novo synthesis of pyrimidine nucleotides." J Biol Chem 252(18);6379-85. PMID: 19472

Cox01: Cox RJ, Wang PSH (2001). "Is N-acetylornithine aminotransferase the real N-succinyl-LL-diaminopimelate aminotransferase in Escherichia coli and Mycobacterium smegmatis?." J. Chem. Soc., Perkin Trans. 1:2006-2008.

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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