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Escherichia coli K-12 substr. MG1655 Pathway: ornithine biosynthesis

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

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Superclasses: Biosynthesis Amino Acids Biosynthesis Individual Amino Acids Biosynthesis Other Amino Acid Biosynthesis

General Background

While the amino acid L-ornithine is not involved directly in protein synthesis, it is an important intermediate in many metabolic pathways of prokaryotes and eukaryotes (see urea cycle, pyoverdine I biosynthesis and gramicidin S biosynthesis). In some bacteria L-ornithine-containing lipids and genes involved in their biosynthesis have been identified, but other bacteria such as Escherichia coli do not contain ornithine lipids (reviewed in [Geiger10]) (see MetaCyc pathway ornithine lipid biosynthesis). In E. coli L-ornithine is a precursor of the amino acid L-arginine and the polyamine putrescine, which is in turn a precursor of the polyamine spermidine.

In this pathway L-ornithine is biosynthesized from L-glutamate via N-acetylated intermediates. The presumed reason for the acetylation is that it prevents the spontaneous cyclization of glutamate derivatives, which leads to L-proline biosynthesis (see proline biosynthesis I), thus keeping the pathways leading to L-arginine and L-proline separate ([Caldovic03] and references therein).

Two alternative pathways have evolved that differ in the way the key intermediate N-acetyl-L-glutamate is formed and in the way the acetyl group is removed from another key intermediate, N-acetyl-L-ornithine. In this pathway, which is less common but is found in the Enterobacteriaceae, N-acetyl-L-glutamate is formed by N-acetyl-L-glutamate synthase and N-acetyl-L-ornithine is hydrolyzed by the enzyme acetylornithine deacetylase, forming L-ornithine and acetate. In the other pathway, which is found in most prokaryotic and eukaryotic microorganisms, the two reactions are linked: the acetyl group which is removed from N-acetyl-L-ornithine is recycled onto L-glutamate, regenerating N-acetyl-L-glutamate (see arginine biosynthesis II (acetyl cycle)).

About This Pathway

In the ornithine biosynthesis pathway of E. coli, L-glutamate is acetylated to N-acetylglutamate by the enzyme N-acetylglutamate synthase, encoded by the argA gene. The acetyl donor for this reaction is acetyl-CoA. N-acetyl-L-glutamate 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, producing L-ornithine and acetate. L-ornithine is a precursor of the amino acid L-arginine, as shown in the pathway link.

Review: Charlier, D. and N. Glansdorff (2004) "Biosynthesis of Arginine and Polyamines." EcoSal [ECOSAL]

Superpathways: arginine biosynthesis I (via L-ornithine) , superpathway of arginine and polyamine biosynthesis

Created 15-Jan-1999 by Iourovitski I , SRI International
Revised 14-Apr-2006 by Caspi R , SRI International
Last-Curated ? 30-Mar-2011 by Fulcher C , 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

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Geiger10: Geiger O, Gonzalez-Silva N, Lopez-Lara IM, Sohlenkamp C (2010). "Amino acid-containing membrane lipids in bacteria." Prog Lipid Res 49(1);46-60. PMID: 19703488

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

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

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

Billheimer76: Billheimer 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

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

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

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.

Cox96: Cox, R. J., Sherwin, W.A., Lam, L.K.P., Vederas, J.C. (1996). "Synthesis and evaluation of novel substrates and inhibitors of N-succinyl-L,L-diaminopimelate aminotransferase (DAP-AT) from Escherichia coli." J. Am. Chem. Soc. 118:7449-7460.

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Eckhardt75: Eckhardt T, Leisinger T (1975). "Isolation and characterization of mutants with a feedback resistant N-acetylglutamate synthase in Escherichia coli K 12." Mol Gen Genet 138(3);225-32. PMID: 1102931

Gil99: Gil F, Ramon-Maiques S, Marina A, Fita I, Rubio V (1999). "N-Acetyl-L-glutamate kinase from Escherichia coli: cloning of the gene, purification and crystallization of the recombinant enzyme and preliminary X-ray analysis of the free and ligand-bound forms." Acta Crystallogr D Biol Crystallogr 1999;55 ( Pt 7);1350-2. PMID: 10393305

GilOrtiz02: Gil-Ortiz F, Fita I, Ramon-Maiques S, Marina A, Rubio V (2002). "A crystallographic glimpse of a nucleotide triphosphate (AMPPNP) bound to a protein surface: external and internal AMPPNP molecules in crystalline N-acetyl-L-glutamate kinase." Acta Crystallogr D Biol Crystallogr 58(Pt 10 Pt 2);1892-5. PMID: 12351849

GilOrtiz03: Gil-Ortiz F, Ramon-Maiques S, Fita I, Rubio V (2003). "The course of phosphorus in the reaction of N-acetyl-L-glutamate kinase, determined from the structures of crystalline complexes, including a complex with an AlF(4)(-) transition state mimic." J Mol Biol 331(1);231-44. PMID: 12875848

GilOrtiz10: Gil-Ortiz F, Ramon-Maiques S, Fernandez-Murga ML, Fita I, Rubio V (2010). "Two crystal structures of Escherichia coli N-acetyl-L-glutamate kinase demonstrate the cycling between open and closed conformations." J Mol Biol 399(3);476-90. PMID: 20403363

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Heimberg90: Heimberg H, Boyen A, Crabeel M, Glansdorff N (1990). "Escherichia coli and Saccharomyces cerevisiae acetylornithine aminotransferase: evolutionary relationship with ornithine aminotransferase." Gene 90(1);69-78. PMID: 2199330

Itikawa68: Itikawa H, Baumberg S, Vogel HJ (1968). "Enzymic basis for a genetic suppression: accumulation and deacylation of N-acetylglutamic gamma-semialdehyde in enterobacterial mutants." Biochim Biophys Acta 159(3);547-50. PMID: 4872548

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Tue Nov 25, 2014, BIOCYC13A.