2.02012-05-31 13:50:24 -06002015-06-03 15:53:56 -0600ECMDB01346M2MDB000347GDP-4-Dehydro-6-deoxy-D-mannoseGDP-4-Dehydro-6-deoxy-D-mannose is an intermediate in fructose and mannose metabolism. GDP-4-Dehydro-6-deoxy-D-mannose is generated by GDP-D-mannose-4,6-dehydratase (GMD). This compound is then converted by the FX protein (GDP-4-keto-6-D-deoxymannose epimerase/GDP-4-keto-6-L-galactose reductase) to GDP-L-fucose. (PMID: 11698403). It is also involved in amino sugar and nucleotide sugar metabolism. (KEGG)GDP-4-Dehydro-6-deoxy-D-mannoseGDP-4-Dehydro-6-deoxy-D-taloseGDP-4-Dehydro-D-rhamnoseGDP-4-Keto-6-D-deoxymannoseGDP-4-keto-6-deoxy-α-D-mannoseGDP-4-keto-6-Deoxy-a-D-mannoseGDP-4-Keto-6-deoxy-alpha-D-mannoseGDP-4-Keto-6-deoxy-D-mannoseGDP-4-keto-6-Deoxy-α-D-mannoseGDP-4-Keto-6-deoxymannoseGDP-4-Oxo-6-deoxy-D-mannoseGDP-4-Oxo-6-deoxymannoseGuanosine diphosphate-4-keto-6-deoxy-D-mannoseGuanosine diphosphoric acid-4-keto-6-deoxy-D-mannoseC16H23N5O15P2587.3258587.066588115[({[(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,4R,6R)-3,4-dihydroxy-6-methyl-5-oxooxan-2-yl]oxy})phosphinic acidgdp-4-keto-6-deoxymannose18186-48-6C[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C=NC3=C2N=C(N)NC3=O)[C@@H](O)[C@@H](O)C1=OInChI=1S/C16H23N5O15P2/c1-4-7(22)9(24)11(26)15(33-4)35-38(30,31)36-37(28,29)32-2-5-8(23)10(25)14(34-5)21-3-18-6-12(21)19-16(17)20-13(6)27/h3-5,8-11,14-15,23-26H,2H2,1H3,(H,28,29)(H,30,31)(H3,17,19,20,27)/t4-,5-,8-,9+,10-,11+,14-,15-/m1/s1PNHLMHWWFOPQLK-BKUUWRAGSA-NSolidCytosollogp-1.28logs-1.97solubility6.35e+00 g/llogp-3.6pka_strongest_acidic1.73pka_strongest_basic-3.7iupac[({[(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,4R,6R)-3,4-dihydroxy-6-methyl-5-oxooxan-2-yl]oxy})phosphinic acidaverage_mass587.3258mono_mass587.066588115smilesC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C=NC3=C2N=C(N)NC3=O)[C@@H](O)[C@@H](O)C1=OformulaC16H23N5O15P2inchiInChI=1S/C16H23N5O15P2/c1-4-7(22)9(24)11(26)15(33-4)35-38(30,31)36-37(28,29)32-2-5-8(23)10(25)14(34-5)21-3-18-6-12(21)19-16(17)20-13(6)27/h3-5,8-11,14-15,23-26H,2H2,1H3,(H,28,29)(H,30,31)(H3,17,19,20,27)/t4-,5-,8-,9+,10-,11+,14-,15-/m1/s1inchikeyPNHLMHWWFOPQLK-BKUUWRAGSA-Npolar_surface_area304.04refractivity116.2polarizability48.01rotatable_bond_count8acceptor_count15donor_count8physiological_charge-2formal_charge0Fructose and mannose metabolismec00051Amino sugar and nucleotide sugar metabolismec00520Metabolic pathwayseco01100Mannose 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.PW000822Metaboliccolanic acid building blocks biosynthesisThe 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).
PW000951MetabolicGDP-L-fucose biosynthesis I (from GDP-D-mannose)PWY-66Specdb::CMs26579Specdb::CMs38034Specdb::CMs282800Specdb::CMs411272Specdb::CMs411273Specdb::CMs411274Specdb::CMs411275Specdb::CMs411276Specdb::CMs411277Specdb::CMs411278Specdb::CMs411279Specdb::CMs411280Specdb::CMs411281Specdb::CMs411282Specdb::CMs411283Specdb::CMs411284Specdb::CMs411285Specdb::CMs411286Specdb::CMs411287Specdb::CMs411288Specdb::CMs411289Specdb::CMs411290Specdb::CMs411291Specdb::CMs411292Specdb::CMs411293Specdb::NmrOneD9222Specdb::NmrOneD9223Specdb::NmrOneD9224Specdb::NmrOneD9225Specdb::NmrOneD9226Specdb::NmrOneD9227Specdb::NmrOneD9228Specdb::NmrOneD9229Specdb::NmrOneD9230Specdb::NmrOneD9231Specdb::NmrOneD9232Specdb::NmrOneD9233Specdb::NmrOneD9234Specdb::NmrOneD9235Specdb::NmrOneD9236Specdb::NmrOneD9237Specdb::NmrOneD9238Specdb::NmrOneD9239Specdb::NmrOneD9240Specdb::NmrOneD9241Specdb::MsMs25670Specdb::MsMs25671Specdb::MsMs25672Specdb::MsMs32228Specdb::MsMs32229Specdb::MsMs32230Specdb::MsMs2798741Specdb::MsMs2798742Specdb::MsMs2798743Specdb::MsMs2883308Specdb::MsMs2883309Specdb::MsMs2883310HMDB01346439446388554C0122216955GDP-4-DEHYDRO-6-DEOXY-D-MANNOSEKeseler, 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-D590.21097882Kanehisa, 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-D114.22080510van 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 370:17-25.17765195Winder, 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 80:2939-2948.18331064Roos, C., Kolmer, M., Mattila, P., Renkonen, R. (2002). "Composition of Drosophila melanogaster proteome involved in fucosylated glycan metabolism." J Biol Chem 277:3168-3175.11698403Oths, Philip J.; Mayer, Robert M.; Floss, Heinz G. Stereochemistry and mechanism of the GDP-mannose dehydratase reaction. Carbohydrate Research (1990), 198(1), 91-100.GDP-mannose 4,6-dehydrataseP0AC88GM4D_ECOLIgmdhttp://ecmdb.ca/proteins/P0AC88.xmlGDP-L-fucose synthaseP32055FCL_ECOLIfclhttp://ecmdb.ca/proteins/P32055.xmlGDP-4-Dehydro-6-deoxy-D-mannose > GDP-4-Oxo-L-fucoseGuanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + WaterR00888GDPMANDEHYDRA-RXNGDP-L-Fucose + NADP <> GDP-4-Dehydro-6-deoxy-D-mannose + NADPH + Hydrogen ionR056921.1.1.271-RXNGDP-L-Fucose + NADP < Hydrogen ion + NADPH + GDP-4-Dehydro-6-deoxy-D-mannose1.1.1.271-RXNGuanosine diphosphate mannose > Water + GDP-4-Dehydro-6-deoxy-D-mannoseGDPMANDEHYDRA-RXNGDP-L-Fucose + NADP > GDP-4-Dehydro-6-deoxy-D-mannose + NADPHR056921.1.1.271-RXNGDP-4-Dehydro-6-deoxy-D-mannose + NADPH + Hydrogen ion + NADPH > GDP-L-Fucose + NADPPW_R002963Guanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + WaterGuanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + Water