2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages II. Dissociation of the inhibitory effects of 2-deoxyglucose on phagocytosis and ATP generation. (1/352)

Macrophages incubated in 2-deoxy-D-glucose (2-dG)-containing medium showed a marked decrease in cellular ATP content, and were unable to ingest IgG- and complement-coated erythrocytes via the corresponding membrane receptors for these ligands. However, the inhibitory effects of 2-dG on Fc- and C3 receptor-mediated phagocytosis were not a consequence of lowered macrophage ATP levels since addition of glucose or mannose to the culture medium restored the capacity of the macrophages to ingest IgG- and C3-coated particles without increasing ATP levels. These results indicate that Fc- and C3 receptor-mediated phagocytosis (opsonin dependent) differs qualitatively from the ingestion of latex and zymosan particles (opsonin independent); they suggest that the same regulatory molecules govern the responses of phagocytic cells to signals initiated by both the Fc and C3 receptors. The possibility that these molecules are regulated by glycosylation is discussed.  (+info)

Structure of the O-specific polysaccharide of a serologically separate strain Proteus penneri 2 from a new proposed serogroup O66. (2/352)

O-specific polysaccharide chain of Proteus penneri strain 2 lipopolysaccharide was studied by full and partial acid hydrolysis, Smith degradation, methylation analysis, and NMR spectroscopy, including two-dimensional rotating-frame NOE spectroscopy (ROESY) and 1H,13C heteronuclear multiple-quantum coherence (HMQC) experiments. Together with D-glucose and 2-acetamido-2-deoxy-D-glucose, the polysaccharide was found to contain two rarely occurring sugars, 6-deoxy-L-talose (L-6dTal) and 2,3-diacetamido-2,3,6-trideoxy-L-mannose (L-RhaNAc3NAc), and the following structure of a non-stoichiometrically O-acetylated tetrasaccharide repeating unit was established: [equation: see text] The O-specific polysaccharide studied has a unique composition and structure and, accordingly, P. penneri 2 is serologically separate among Proteus strains. Therefore, we propose for P. penneri 2 a new Proteus O-serogroup O66 where this strain is at present the single representative.  (+info)

Interactions on 3-deoxy and 6-deoxy derivatives of N-acetyl-D-glucosamine with hen lysozyme. (3/352)

The interactions of deoxy derivatives of GlcNAc, 6-deoxy-GlcNAc, and 3-deoxy-GlcNAc with hen egg-white lysozyme [EC] were studied at various pH's by measuring the changes in the circular dichroic (CD) band at 295 nm. It was shown that 6-deoxy-GlcNAc and 3-deoxy-GlcNAc bind at subsite C of lysozyme and compete with GlcNAc. The pH dependence of the binding constant of 6-deoxy-GlcNAc was the same as that of GlcNAc. On the other hand, the binding constants of 3-deoxy-GlcNAc were 3--10 times smaller than those of GlcNAc in the pH range from 3 to 9. X-ray crystallographic studies show that O(6) and O(3) of GlcNAc at subsite C are hydrogen-bonded to the indole NH's of Trp 62 and Trp 63, respectively, but the above results indicate that Trp 63, not Trp 62, is important for the interaction of GlcNAc with lysozyme.  (+info)

2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages. I. Description of the inhibitory effect. (4/352)

Incubation of normal or thioglycollate-elicited mouse peritoneal macrophages with 2-deoxy-D-glucose (2-dG) inhibits the capacity of these macrophages to phagocytize IgG- or complement-coated particles via their Fc and C3 receptors. 2-dG has no inhibitory effect on the capacity of these macrophages to phagocytize latex or zymosan particles, which are ingested in the absence of specific opsonins, and it does not inhibit binding of IgG- or C3-coated particles to their respective receptors on the macrophage's plasma membrane. 2-dG exerts its inhibitory effect on the macrophage and not on the opsonized particle. The inhibition is independent of particle size, occurs within 15-30 min of addition of this glucose analogue to the medium at 37 degrees C, cannot be overcome by supra-agglutinating amounts of opsonizing antibody, and is completely reversible by substitution of 5.5 mM glucose for 50 mM 2-dG in the medium. Addition of equimolar amounts of glucose or mannose, but not of fructose, galactose, fucose, or glucosamine, to medium containing 50 mM 2-dG results in substantial reversal of the inhibitory effect of 2-dG on Fc and C3 receptor mediated phagocytosis.  (+info)

Interference of nucleoside diphosphate derivatives of 2-deoxy-D-glucose with the glycosylation of virus-specific glycoproteins in vivo. (5/352)

The predominant effect of 2-deoxy-D-glucose on chick embryo cells infected with Semliki Forest virus is an interference with glycosylation of virus-specific glycoproteins; this results in a block of synthesis of infectious virus. Incorporation of radioactive mannose is blocked severely in the presence of 2-deoxyglucose in the cultural medium although it is readily phosphorylated and subsequently activated by GTP to yield GDP-mannose, which accumulates under these conditions. The intracellular concentrations of GDP-mannose and UDP-N-acetyl-D-hexosamine are not reduced in the presence of the inhibitor. An equimolar concentration of mannose in the cultural medium competes with the inhibitory effect of the deoxysugar and drops the cellular pool of GDP-2-deoxy-D-glucose below the level of detection, at the same time restoring the synthesis of infectious virus. When the intracellular concentration of UDP-2-deoxyglucose is reduced by addition of glucose into the cultural medium the inhibition of virus synthesis by the deoxysugar and the concentration of GDP-2-deoxyglucose within the cells remain near to the values when the inhibitor is present alone. It is concluded that among the metabolites of 2-deoxyglucose which occur in vivo after addition of 2-deoxyglucose to the culture medium, GDP-2-deoxyglucose is the agent responsible for inhibition of glycosylation of viral glycoproteins.  (+info)

[18F]-labeled 3-deoxy-3-fluoro-D-glucose: synthesis and preliminary biodistribution data. (6/352)

A cyclotron target system for the production of anhydrous [18F] fluoride ion has been developed and used for the synthesis of carrier-free [18F]-3-deoxy-3fluoro-D-glucose (3-FDG). The synthesis is sufficiently rapid and efficient to allow production of usable amounts of 3-FDG with a 6-MeV cyclotron. Preliminary animal studies show that 3-FDG is in fact a glucose analog.  (+info)

The effect of 2-deoxy-D-glucose and D-glucose on the efferent discharge rate of sympathetic nerves. (7/352)

Efferent discharges were recorded from nerve filaments dissected from the adrenal and renal nerves in the rabbit. 2. An increase in discharge rate was observed in the adrenal nerve filaments following I.V. administration of 2-deoxy-D-glucose (2-DG). No change in discharge rate after 2-DG infusion was observed in the renal nerve filaments. 3. A decrease in discharge rate of the adrenal nerve filaments was observed after I.V. injection of glucose, but there was no change in the activity of renal nerve filaments. 4. Transection of the spinal cord abolished the adrenal nerve response to the systemic administration of 2-DG and glucose. 5. It is suggested that there might be a pathway from the hypothalmic area to the adrenal nerve cells of the spinal cord, but not to the renal nerve cells, through which activity of the adrenal nerve might be changed in response to 2-DG and glucose infusion.  (+info)

Thymidine diphosphate-6-deoxy-L-lyxo-4-hexulose reductase synthesizing dTDP-6-deoxy-L-talose from Actinobacillus actinomycetemcomitans. (8/352)

The serotype c-specific polysaccharide antigen of Actinobacillus actinomycetemcomitans NCTC 9710 contains an unusual sugar, 6-deoxy-L-talose, which has been identified as a constituent of cell wall components in some bacteria. Two genes coding for thymidine diphosphate (dTDP)-6-deoxy-L-lyxo-4-hexulose reductases were identified in the gene cluster required for biosynthesis of serotype c-specific polysaccharide. Both dTDP-6-deoxy-L-lyxo-4-hexulose reductases were overproduced and purified from Escherichia coli transformed with the plasmids containing these genes. The sugar nucleotides converted by both reductases were purified by reversed-phase high performance liquid chromatography and identified by (1)H nuclear magnetic resonance and gas-liquid chromatography. The results indicated that one of two reductases produced dTDP-6-deoxy-L-talose and the other produced dTDP-L-rhamnose (dTDP-6-deoxy-L-mannose). The amino acid sequence of the dTDP-6-deoxy-L-lyxo-4-hexulose reductase forming dTDP-6-deoxy-L-talose shared only weak homology with that forming dTDP-L-rhamnose, despite the fact that these two enzymes catalyze the reduction of the same substrate and the products are determined by the stereospecificity of the reductase activity. Neither the gene for dTDP-6-deoxy-L-talose biosynthesis nor its corresponding protein product has been found in other bacteria; this biosynthetic pathway is identified here for the first time.  (+info)