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Pathway Description
Amino Sugar and Nucleotide Sugar Metabolism III
Escherichia coli
Metabolic Pathway
The synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction catalyzed by N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate. N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound can either be isomerized or deaminated into Beta-D-fructofuranose 6-phosphate through a glucosamine-fructose-6-phosphate aminotransferase and a glucosamine-6-phosphate deaminase respectively.
Glucosamine 6-phosphate undergoes a reversible reaction to glucosamine 1 phosphate through a phosphoglucosamine mutase. This compound is then acetylated through a bifunctional protein glmU to produce a N-Acetyl glucosamine 1-phosphate.
N-Acetyl glucosamine 1-phosphate enters the nucleotide sugar synthesis by reacting with UTP and hydrogen ion through a bifunctional protein glmU releasing pyrophosphate and a Uridine diphosphate-N-acetylglucosamine.This compound can either be isomerized into a UDP-N-acetyl-D-mannosamine or undergo a reaction with phosphoenolpyruvic acid through UDP-N-acetylglucosamine 1-carboxyvinyltransferase releasing a phosphate and a UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate.
UDP-N-acetyl-D-mannosamine undergoes a NAD dependent dehydrogenation through a UDP-N-acetyl-D-mannosamine dehydrogenase, releasing NADH, a hydrogen ion and a UDP-N-Acetyl-alpha-D-mannosaminuronate, This compound is then used in the production of enterobacterial common antigens.
UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate is reduced through a NADPH dependent UDP-N-acetylenolpyruvoylglucosamine reductase, releasing a NADP and a UDP-N-acetyl-alpha-D-muramate. This compound is involved in the D-glutamine and D-glutamate metabolism.
References
Amino Sugar and Nucleotide Sugar Metabolism III References
Blackburn P, Ferdinand W: The concerted inactivation of Escherichia coli uridine diphosphate galactose 4-epimerase by sugar nucleotide together with a free sugar. Biochem J. 1976 May 1;155(2):225-9. doi: 10.1042/bj1550225.
Pubmed: 779771
Aidelberg G, Towbin BD, Rothschild D, Dekel E, Bren A, Alon U: Hierarchy of non-glucose sugars in Escherichia coli. BMC Syst Biol. 2014 Dec 24;8:133. doi: 10.1186/s12918-014-0133-z.
Pubmed: 25539838
Gonzalez GM, Durica-Mitic S, Hardwick SW, Moncrieffe MC, Resch M, Neumann P, Ficner R, Gorke B, Luisi BF: Structural insights into RapZ-mediated regulation of bacterial amino-sugar metabolism. Nucleic Acids Res. 2017 Oct 13;45(18):10845-10860. doi: 10.1093/nar/gkx732.
Pubmed: 28977623
Plumbridge J: Regulation of the Utilization of Amino Sugars by Escherichia coli and Bacillus subtilis: Same Genes, Different Control. J Mol Microbiol Biotechnol. 2015;25(2-3):154-67. doi: 10.1159/000369583. Epub 2015 Jul 9.
Pubmed: 26159076
Skarbek K, Milewska MJ: Biosynthetic and synthetic access to amino sugars. Carbohydr Res. 2016 Nov 3;434:44-71. doi: 10.1016/j.carres.2016.08.005. Epub 2016 Aug 24.
Pubmed: 27592039
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