2.0 2012-05-31 13:46:37 -0600 2015-06-03 15:53:47 -0600 ECMDB01163 M2MDB000279 Guanosine diphosphate mannose GDP-mannose is a nucleoside diphosphate sugar that is important in the production of fucosylated oligosaccharides. GDP-mannose is transformed to GDP-fucose via three enzymatic reactions carried out by two proteins, GDP-mannose 4,6-dehydratase (GMD) and a second enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase. GDP-mannose 4,6-dehydratase (EC 4.2.1.47) catalyzes the chemical reaction: GDP-mannose <--> GDP-4-dehydro-6-deoxy-D-mannose + H2O. The epimerase converts the GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose. (PMID: 12651883). GDP-mannose is also synthesized from mannose 1-phosphate via the enzyme ATP-mannose-1-phosphate-guanyltransferase and GTP. GDP Mannose GDP-D-Mannose GDP-Glucose GDP-Man GDP-Mannose GDP-α-D-mannose Guanosine Diphosphate Mannose Guanosine diphosphomannose Guanosine diphosphoric acid mannose Guanosine pyrophosphate mannose Guanosine pyrophosphoric acid mannose C16H25N5O16P2 605.3411 605.077152801 [({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})phosphinic acid guanosine diphosphomannose 3123-67-9 NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(=O)O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)C(=O)N1 InChI=1S/C16H25N5O16P2/c17-16-19-12-6(13(28)20-16)18-3-21(12)14-10(26)8(24)5(34-14)2-33-38(29,30)37-39(31,32)36-15-11(27)9(25)7(23)4(1-22)35-15/h3-5,7-11,14-15,22-27H,1-2H2,(H,29,30)(H,31,32)(H3,17,19,20,28)/t4-,5-,7-,8-,9+,10-,11+,14-,15-/m1/s1 MVMSCBBUIHUTGJ-GDJBGNAASA-N Solid Cytosol logp -1.76 ALOGPS logs -1.89 ALOGPS solubility 7.77e+00 g/l ALOGPS logp -5.3 ChemAxon pka_strongest_acidic 1.73 ChemAxon pka_strongest_basic -3.6 ChemAxon iupac [({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})phosphinic acid ChemAxon average_mass 605.3411 ChemAxon mono_mass 605.077152801 ChemAxon smiles NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(=O)O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)C(=O)N1 ChemAxon formula C16H25N5O16P2 ChemAxon inchi InChI=1S/C16H25N5O16P2/c17-16-19-12-6(13(28)20-16)18-3-21(12)14-10(26)8(24)5(34-14)2-33-38(29,30)37-39(31,32)36-15-11(27)9(25)7(23)4(1-22)35-15/h3-5,7-11,14-15,22-27H,1-2H2,(H,29,30)(H,31,32)(H3,17,19,20,28)/t4-,5-,7-,8-,9+,10-,11+,14-,15-/m1/s1 ChemAxon inchikey MVMSCBBUIHUTGJ-GDJBGNAASA-N ChemAxon polar_surface_area 327.43 ChemAxon refractivity 118.51 ChemAxon polarizability 48.72 ChemAxon rotatable_bond_count 9 ChemAxon acceptor_count 16 ChemAxon donor_count 10 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Fructose and mannose metabolism ec00051 Ascorbate and aldarate metabolism ec00053 Amino sugar and nucleotide sugar metabolism ec00520 Metabolic pathways eco01100 Amino sugar and nucleotide sugar metabolism II 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 through a 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 is then deaminased into Beta-D-fructofuranose 6-phosphate through a glucosamine-6-phosphate deaminase. The beta-D-fructofuranose 6 -phosphate is isomerized in a reversible reaction into an alpha-D-mannose 6-phosphate. This compound can also be introduced into the cell from the periplasmic space through a mannose PTS permease that phosphorylates an alpha-D-mannose. Alpha-D-mannose 6-phosphate undergoes a reversible reaction through a phosphomannomutase to produce an alpha-D-mannose 1-phosphate. The alpha-D-mannose 1-phosphate enters the nucleotide sugar metabolism through a reaction with GTP producing a GDP-mannose and releasing a pyrophosphate, all through a mannose-1-phosphate guanylyltransferase. GDP-mannose is then dehydrated to produce GDP-4-dehydro-6-deoxy-alpha-D-mannose through a GDP-mannose 4,6-dehydratase. This compound is then used to synthesize GDP-Beta-L-fucose through a NADPH dependent GDP-L-fucose synthase. Alpha-D-glucose is introduced into the cytoplasm through a glucose PTS permease, which phosphorylates the compound in order to produce an alpha-D-glucose 6-phosphate. This compound is then modified through a phosphoglucomutase 1 to yield alpha-D-glucose 1-phosphate. This compound can either be adenylated to produce ADP-glucose or uridylylated to produce galactose 1-phosphate through glucose-1-phosphate adenyllyltransferase and galactose-1-phosphate uridylyltransferase respectively. PW000887 Metabolic Mannose Metabolism D-mannose can serve as a total source of carbon and energy for growth of E. coli. Alpha-D-mannose is introduced into the cytoplasm through a mannose PTS permease. Because mannose is taken up via a phosphotransferase system (PTS), the first intracellular species is D-mannose-6-phosphate. mannose-6-phosphate isomerase converts D-mannose-6-phosphate to D-fructose-6-phosphate, an intermediate of glycolysis, and hence it flows through the pathways of central metabolism to satisfy the cell's need for precursor metabolites, reducing power, and metabolic energy. The first two enzymes in the pathway (SEE VERTICAL SECTION) catalyze isomerizations that interconvert phosphorylated aldohexoses (β-D-glucose-6-phosphate, D-mannose-6-phosphate) and phosphorylated ketohexoses (D-fructose-6-phosphate). The reaction catalyzed by mannose-6-phosphate isomerase that produces D-mannose-6-phosphate is the first committed step in the biosynthesis of the activated mannose donor GDP-α-D-mannose. D-mannose-6-phosphate is then converted to GDP-D-mannose by the interaction of phosphomannomutase and mannose-1-phosphate guanylyltransferase . As for the bottom part L-fucose is biosynthesized as the sugar nucleotide GDP-L-fucose. Its biosynthesis from GDP-D-mannose begins with dehydration of this compound to GDP-4-dehydro-6-deoxy-D-mannose by the product of gene gmd. Then the bifunctional GDP-fucose synthase catalyzes the two-step (epimerase/reductase) synthesis of GDP-fucose from GDP-4-dehydro-6-deoxy-D-mannose via a GDP-4-dehydro-6-L-deoxygalactose intermediate. L-fucose is then incorporated into the colanic acid building blocks biosynthesis pathway. PW000822 Metabolic colanic acid building blocks biosynthesis The colonic acid building blocks biosynthesis starts with a Beta-D-Glucose undergoing a transport reaction mediated by a glucose PTS permease. The permease phosphorylates the Beta-D-Glucose, producing a Beta-D-Glucose 6-phosphate. This compound can either change to an Alpha-D-Glucose 6-phosphate spontaneously or into a fructose 6-phosphate through a glucose-6-phosphate isomerase. The latter compound can also be present in E.coli through the interaction of D-fructose and a mannose PTS permease which phosphorylate the D-fructose. Fructose 6-phosphate interacts in a reversible reaction with mannose-6-phosphate isomerase in order to produce a Alpha-D-mannose 6-phosphate. This compound can also be present in E.coli through the interaction of Alpha-D-mannose and a mannose PTS permease which phosphorylates the alpha-D-mannose. Alpha-D-mannose 6-phosphate interacts in a reversible reaction with a phosphomannomutase to produce a alpha-D-mannose 1-phosphate. This compound in turn with a hydrogen ion and gtp undergoes a reaction with a mannose-1-phosphate guanylyltransferase, releasing a pyrophosphate and producing a guanosine diphosphate mannose. Guanosine diphosphate mannose interacts with gdp-mannose 4,6-dehydratase releasing a water, and gdp-4-dehydro-6-deoxy-D-mannose. This compound in turn with hydrogen ion and NADPH interact with GDP-L-fucose synthase releasing NADP and producing a GDP-L-fucose. The Alpha-D-Glucose 6-phosphate interacts in a reversible reaction with phosphoglucomutase-1 to produce a alpha-D-glucose 1-phosphate. This in turn with UTP and hydrogen ion interact with UTP--glucose-1-phosphate uridyleltransferase releasing a pyrophosphate and UDP-glucose. UDP-glucose can either interact with galactose-1-phosphate uridylyltransferase to produce a UDP-galactose or in turn with NAD and water interact with UDP-glucose 6-dehydrogenase releasing a NADH and a hydrogen ion and producing a UDP-glucuronate. GDP-L-fucose, UDP-glucose, UDP-galactose and UDP-glucuronate are sugars that need to be activated in the form of nucleotide sugar prior to their assembly into colanic acid, also known as M antigen. Colanic acid is an extracellular polysaccharide which has been linked to a cluster of 19 genes(wca). PW000951 Metabolic GDP-mannose biosynthesis PWY-5659 GDP-L-fucose biosynthesis I (from GDP-D-mannose) PWY-66 Specdb::CMs 9956 Specdb::CMs 37952 Specdb::CMs 475905 Specdb::CMs 475906 Specdb::CMs 475907 Specdb::CMs 475908 Specdb::CMs 475909 Specdb::CMs 475910 Specdb::CMs 475911 Specdb::CMs 475912 Specdb::CMs 475913 Specdb::CMs 475914 Specdb::CMs 475915 Specdb::CMs 475916 Specdb::CMs 475917 Specdb::CMs 475918 Specdb::CMs 475919 Specdb::CMs 475920 Specdb::CMs 475921 Specdb::CMs 475922 Specdb::CMs 475923 Specdb::CMs 475924 Specdb::CMs 475925 Specdb::CMs 475926 Specdb::CMs 475927 Specdb::NmrOneD 21282 Specdb::NmrOneD 21283 Specdb::NmrOneD 21284 Specdb::NmrOneD 21285 Specdb::NmrOneD 21286 Specdb::NmrOneD 21287 Specdb::NmrOneD 21288 Specdb::NmrOneD 21289 Specdb::NmrOneD 21290 Specdb::NmrOneD 21291 Specdb::NmrOneD 21292 Specdb::NmrOneD 21293 Specdb::NmrOneD 21294 Specdb::NmrOneD 21295 Specdb::NmrOneD 21296 Specdb::NmrOneD 21297 Specdb::NmrOneD 21298 Specdb::NmrOneD 21299 Specdb::NmrOneD 21300 Specdb::NmrOneD 21301 Specdb::MsMs 23411 Specdb::MsMs 23412 Specdb::MsMs 23413 Specdb::MsMs 30209 Specdb::MsMs 30210 Specdb::MsMs 30211 Specdb::MsMs 1470784 Specdb::MsMs 1471120 Specdb::MsMs 2226603 Specdb::MsMs 2228143 Specdb::MsMs 2228918 Specdb::MsMs 2230503 Specdb::MsMs 2231263 Specdb::MsMs 2232960 Specdb::MsMs 2757834 Specdb::MsMs 2757835 Specdb::MsMs 2757836 Specdb::MsMs 2948451 Specdb::MsMs 2948452 Specdb::MsMs 2948453 HMDB01163 732 17372 C00096 15820 GDP-MANNOSE GDD Guanosine diphosphate mannose Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Becker, D. J., Lowe, J. B. (2003). "Fucose: biosynthesis and biological function in mammals." Glycobiology 13:41R-53R. 12651883 Huang, Gang-Liang; Liu, Xiang; Zhang, Hou-Cheng; Wang, Peng-George. A facile two-step chemo-enzymatic synthesis of GDP-mannose. Letters in Organic Chemistry (2006), 3(9), 668-669. GDP-mannose 4,6-dehydratase P0AC88 GM4D_ECOLI gmd http://ecmdb.ca/proteins/P0AC88.xml Mannose-1-phosphate guanylyltransferase P24174 MANC_ECOLI manC http://ecmdb.ca/proteins/P24174.xml GDP-mannose mannosyl hydrolase P32056 NUDD_ECOLI nudD http://ecmdb.ca/proteins/P32056.xml GDP-mannose pyrophosphatase nudK P37128 NUDK_ECOLI nudK http://ecmdb.ca/proteins/P37128.xml Guanosine diphosphate + Hydrogen ion + D-Mannose 1-phosphate > Guanosine diphosphate mannose + Phosphate Guanosine diphosphate mannose + Water > Guanosine diphosphate + Hydrogen ion + D-Mannose GDPMANMANHYDRO-RXN Guanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + Water R00888 GDPMANDEHYDRA-RXN Guanosine diphosphate mannose + Water > Guanosine monophosphate +2 Hydrogen ion + D-Mannose 1-phosphate RXN0-5108 Guanosine triphosphate + D-Mannose 1-phosphate <> Pyrophosphate + Guanosine diphosphate mannose R00885 2.7.7.13-RXN Guanosine diphosphate mannose + Water > Hydrogen ion + Guanosine monophosphate + D-Mannose 1-phosphate RXN0-5108 Hydrogen ion + D-Mannose 1-phosphate + Guanosine triphosphate > Guanosine diphosphate mannose + Pyrophosphate 2.7.7.13-RXN Guanosine diphosphate mannose > Water + GDP-4-Dehydro-6-deoxy-D-mannose GDPMANDEHYDRA-RXN Guanosine diphosphate mannose + Water > Guanosine diphosphate + D-Mannose Guanosine triphosphate + Alpha-D-mannose 1-phosphate > Pyrophosphate + Guanosine diphosphate mannose Guanosine diphosphate mannose + Water > Guanosine monophosphate + Alpha-D-mannose 1-phosphate D-Mannose 1-phosphate + Guanosine triphosphate + Hydrogen ion > Pyrophosphate + Guanosine diphosphate mannose PW_R002961 α-D-mannose 1-phosphate + Guanosine triphosphate + Hydrogen ion > Guanosine diphosphate mannose + Pyrophosphate PW_R003361 Guanosine diphosphate mannose > Water + GDP-4-dehydro-6-deoxy-α-D-mannose PW_R003362 Guanosine diphosphate mannose > GDP-4-Dehydro-6-L-deoxygalactose + GDP-4-Dehydro-6-L-deoxygalactose PW_R005171 Guanosine triphosphate + D-Mannose 1-phosphate <> Pyrophosphate + Guanosine diphosphate mannose Guanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + Water Guanosine triphosphate + D-Mannose 1-phosphate <> Pyrophosphate + Guanosine diphosphate mannose Guanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + Water