If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Proteinogenic Amino Acids Biosynthesis → L-arginine Biosynthesis|
The biosynthesis of L-arginine in both prokaryotes and eukaryotes 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. In Escherichia coli the L-arginine biosynthetic genes are scattered in several units of expression on the chromosome and are not strictly coordinated. Synthesis of the L-arginine biosynthetic enzymes is repressed by L-arginine under control of the arginine repressor encoded by the argR gene, forming the arginine regulon [Caldara06, MAAS64]. In stationary phase cultures, positive control by RpoS is also required for full control of arginine biosynthesis [Weerasinghe06]. The initial steps in the L-arginine biosynthesis pathway proceed via N-acetylated intermediates to L-ornithine, as shown here and in pathway L-ornithine biosynthesis. The presumed reason for the acetylation is that it prevents the spontaneous cyclization of L-glutamate derivatives, which leads to L-proline biosynthesis (see L-proline biosynthesis I) thus keeping the pathways leading to L-arginine and L-proline separate ([Caldovic03] and references therein).
In microorganisms 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 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 L-arginine biosynthesis II (acetyl cycle)). In a third pathway found in several eubacteria N-acetyl-L-ornithine is transcarbamylated directly to N-acetyl-L-citrulline, followed by deacetylation to L-citrulline (see pathway L-arginine biosynthesis III (via N-acetyl-L-citrulline)) (reviewed in [Lu06a]).
About This Pathway
In this pathway L-glutamate is acetylated to the key intermediate N-acetyl-glutamate by the enzyme N-acetyl-glutamate synthase, encoded by the argA gene. The acetyl donor for this reaction is acetyl-CoA. N-acetyl-glutamate is then converted in three enzymatic steps to a second key intermediate, N-acetyl-L-ornithine. In the fifth step the acetyl group is then hydrolytically removed by the enzyme acetylornithine deacetylase encoded by the argE gene, producing acetate and the L-arginine precursor L-ornithine. L-ornithine is combined with carbamoyl-phosphate to form L-citrulline, which is converted in two steps to L-arginine. Carbamoyl-phosphate is also a precursor in de novo pyrimidine biosynthesis (see superpathway of pyrimidine ribonucleotides de novo biosynthesis).
The last three steps complete the assembly of the guanidino group of L-arginine from carbamoyl-phosphate and the amino group of L-aspartate. Pathway enzyme regulation occurs via L-arginine feedback inhibition of N-acetylglutamate synthase, and via allosteric activation of carbamoyl phosphate synthetase by L-ornithine. Allosteric inhibition of this enzyme by uridine 5'-phosphate balances the distribution of carbamoyl-phosphate in the arginine and pyrimidine biosynthetic pathways. A molecular kinetic model for arginine biosynthesis in E. coli that was supported by experimental measurements has been developed. The model took into account the complex genetic and metabolic regulatory network including de novo pyrimidine biosynthesis [Caldara08]].
In E. coli L-arginine is not only utilized in protein synthesis, but also as a precursor for the polyamines putrescine and subsequently spermidine (see putrescine biosynthesis I and the pathway link). This putrescine pathway is used when L-arginine concentrations are high enough to inhibit L-ornithine synthesis, which prevents the conversion of L-ornithine to putrescine (as in putrescine biosynthesis III) (reviewed in [Lu06a]).
Review: Charlier, D. and N. Glansdorff (2004) "Biosynthesis of Arginine and Polyamines." EcoSal 188.8.131.52 [ECOSAL]
Superpathways: superpathway of arginine and polyamine biosynthesis
Subpathways: L-ornithine biosynthesis
Caldara06: Caldara M, Charlier D, Cunin R (2006). "The arginine regulon of Escherichia coli: whole-system transcriptome analysis discovers new genes and provides an integrated view of arginine regulation." Microbiology 152(Pt 11);3343-54. PMID: 17074904
Caldara08: Caldara M, Dupont G, Leroy F, Goldbeter A, De Vuyst L, Cunin R (2008). "Arginine biosynthesis in Escherichia coli: experimental perturbation and mathematical modeling." J Biol Chem 283(10);6347-58. PMID: 18165237
Weerasinghe06: Weerasinghe JP, Dong T, Schertzberg MR, Kirchhof MG, Sun Y, Schellhorn HE (2006). "Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli." BMC Microbiol 6;14. PMID: 16504055
Anderson75a: 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
Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699
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
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
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
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: 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
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
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
Cox01a: 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.
Delannay99: Delannay S, Charlier D, Tricot C, Villeret V, Pierard A, Stalon V (1999). "Serine 948 and threonine 1042 are crucial residues for allosteric regulation of Escherichia coli carbamoylphosphate synthetase and illustrate coupling effects of activation and inhibition pathways." J Mol Biol 286(4);1217-28. PMID: 10047492
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
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