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 [Lu06]).
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 [Lu06]).
Review: Charlier, D. and N. Glansdorff (2004) "Biosynthesis of Arginine and Polyamines." EcoSal 184.108.40.206 [ECOSAL]
Superpathways: superpathway of arginine and polyamine biosynthesis
Subpathways: L-ornithine biosynthesis
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