If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Proteinogenic Amino Acids Biosynthesis → L-arginine Biosynthesis|
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 126.96.36.199, amino-acid N-acetyltransferase. A second key intermediate downstream, N-acetyl-L-ornithine, is hydrolyzed by the enzyme EC 188.8.131.52, 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 184.108.40.206, 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 220.127.116.11, 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
Unification Links: EcoCyc:ARGSYN-PWY
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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
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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
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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
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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.
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.
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