Disease relevance of fucose

• Colonization of germ-free mice with Bacteroides thetaiotaomicron, a component of this flora, restored the fucosylation program, whereas an isogenic strain carrying a transposon insertion that disrupts its ability to use L-fucose as a carbon source did not [1].
• Combinations of serum protein-bound carbohydrates, particularly L-fucose and sialic acid, and, in addition, CEA, appear to have promise as potential biomarkers for following the course of the disease in patients with metastatic breast cancer [2].
• Therefore, colitose (3-deoxy-L-fucose), a unique sugar present in the O-antigen of E. coli O111:B4 with structural similarity to L-fucose, is the most probable candidate for a specific ligand of tachylectin-4 [3].
• Streptomyces sp. 142, isolated from a soil sample, produced alpha-fucosidase when cultured in the presence of L-fucose [4].
• The bacterium Ralstonia solanacearum, which is distributed worldwide and causes lethal wilt in many agricultural crops, was shown to produce a potent L-fucose-binding lectin, R. solanacearum lectin, a small protein of 90 amino acids with a tandem repeat in its amino acid sequence [5].

High impact information on fucose

• An Arabidopsis thaliana mutant (mur1) has less than 2 percent of the normal amounts of L-fucose in the primary cell walls of aerial portions of the plant [6].
• As documented by intravital microscopy of small venules in the rabbit mesentery and tenuissimus muscle, leukocyte rolling was rapidly and profoundly reduced by intravenous treatment with the polysaccharide fucoidin, a homopolymer of sulfated L-fucose known to block the function of the leukocytic "rolling receptor" L-selectin [7].
• We have recently shown that the simple sugars L-fucose and D-mannose, and an L-fucose-rich polysaccharide (fucoidin), can inhibit this adhesive interaction in vitro [8].
• Using an in vitro assay to measure the adhesive interaction between lymphocytes and postcapillary venules, we have found that L-fucose, D mannose, and the L-fucose-rich, sulfated polysaccharide fucoidin specifically inhibit this binding interaction [9].
• We have used a gnotobiotic mouse model to show that Bacteroides thetaiotaomicron, a component of the intestinal microflora of mice and humans, uses a repressor, FucR, as a molecular sensor of L-fucose availability [10].

Chemical compound and disease context of fucose

• The nonhomologous sugar-H+ symporters for L-rhamnose (RhaT), L-fucose (FucP) and lactose (LacY) in E. coli are insensitive to forskolin [11].
• The L-fucose model system may therefore serve as an experimental tool to elucidate the pathophysiological role of isolated myo-inositol depletion and its consequences in the multifactorial pathogenesis of diabetic neuropathy [12].
• Unlike the effect of chronic exposure of neuroblastoma cells to medium containing 30 mM glucose, the resting membrane potential of neuroblastoma cells is not altered by chronic exposure of the cells to 30 mM L-fucose [13].
• We observed that L-fucose could suppress the skin reaction of allergic contact dermatitis induced by dinitrochlorobenzene [14].
• Decreased myo-inositol uptake is associated with reduced bradykinin-stimulated phosphatidylinositol synthesis and diacylglycerol content in cultured neuroblastoma cells exposed to L-fucose [15].

Biological context of fucose

• L-Fucose-terminated glycoconjugates are recognized by pinocytosis receptors on macrophages [16].
• FucR coordinates expression of an operon encoding enzymes in the L-fucose metabolic pathway with expression of another locus that regulates production of fucosylated glycans in intestinal enterocytes [10].
• D-Mannose, L-fucose, and N-acetyl-D-glucosamine failed to inhibit hemagglutination at 0.2 M [17].
• Motor nerve conduction velocity was significantly slower in rats fed a 10 or 20% L-fucose diet [18].
• Accumulation of L-fucose at 4 degrees C and in the presence of colchicine and cytochalasin D rules out receptor-mediated endocytosis as an uptake mechanism [19].

Anatomical context of fucose

• A series of neoglycoproteins, including L-fucose-albumin, were tested as inhibitors of uptake of 125I-labeled beta-glucuronidase into macrophages [16].
• In vitro, 125I-labeled L-fucose-albumin is taken up into rat or rabbit alveolar macrophages by receptor-mediated pinocytosis [16].
• The fucosylation defect in LAD II fibroblasts can be corrected by addition of L-fucose to the culture medium [20].
• Administration of oral L-fucose to the patient produced molecular and clinical responses, as measured by the appearance of selectin ligands, normalization of neutrophil counts, and prevention of infectious recurrence [21].
• The isolation and characterization of endogenous lectins with specificities for lactose, L-fucose, and D-mannose from U937 controls and TPA-differentiated U937 cells demonstrated marked differences in either the pattern and the distribution of these sugar-specific carbohydrate-binding proteins [22].

Associations of fucose with other chemical compounds

• Here we investigate the effects of the naturally occurring threonine-linked L-fucose moiety on the structure, dynamics and stability of the proteinase inhibitor PMP-C (Pars intercerebralis major peptide C) [23].
• Sera from H normal, secretors and nonsecretors (H/-, Se/- and H/-, se/se), as well as from H-deficient secretors (h/h, Se/- or Bombay secretors) contain enzyme(s) for the transfer of L-fucose in the alpha-configuration to the 2-position of suitable beta-D-galactopyranosyl units [24].
• Reduced motor nerve conduction velocity and Na(+)-K(+)-ATPase activity in rats maintained on L-fucose diet. Reversal by myo-inositol supplementation [18].
• We substituted different sugars for the glucuronic acids of glycyrrhizin and found the L-fucose derivative to be the most active in vitro and in vivo [25].
• However, blastocyst formation was inhibited to various extents by high nonphysiological concentrations (50 mM) of D-glucose, D-mannose, L-fucose, D-arabinose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, alpha-lactose, 25 mM-alpha-melibionic acid and by 2 mg/ml fucoidin, ovine mucin and desialylated ovine mucin [26].

Gene context of fucose

• The mur1 mutant of Arabidopsis is deficient in L-fucose in the shoot and is rescued by growth in the presence of exogenously supplied L-fucose [27].
• Based on sequence similarities to a bacterial gene involved in capsule synthesis we have cloned a gene from Arabidopsis, now designated GER1, which encodes a bifunctional 3, 5-epimerase-4-reductase in L-fucose synthesis [28].
• Upon consideration of the transductional nature of these phage classes, we are proposing that the gene order for the L-fucose utilization system is dar, fucA, (lambda), fucC [29].
• Stimulation of beta 2m mRNA by Cuprophan was stereospecifically diminished by 5 mM L-fucose [30].
• Neither CEA nor L-fucose were found to be of value in screening for mammary cancer [31].

Analytical, diagnostic and therapeutic context of fucose

• 125I-Labeled L-fucose-albumin complex and rat preputial beta-glucuronidase are rapidly cleared from plasma after intravenous infusion [16].
• L-fucose metabolism in mammals. Purification of pork liver 2-keto-3-deoxy-L-fuconate:NAD+ oxidoreductase by NAD+-Agarose affinity chromatography [32].
• Accordingly, the migration enhancement factor (MEF) found in spleen cell culture supernatants appeared to depend on L-fucose conjugated to some protein carrier because MEF was non-dialyzable [33].
• The AMAC-labeled five neutral monosaccharide mixture (D-glucose (Glc), D-mannose, D-galactose, L-fucose, and D-xylose) or two amino monosaccharide mixture (N-acetyl-D-glucosamine and N-acetyl-D-galactosamine) were well separated at pH 8.5 and 0.5% w/v methylcellulose of 200 mM borate buffer conditions using microchip electrophoresis [34].
• Autoradiography demonstrated high levels of radioactive L-fucose in the resultant 9L tumors but very little L-fucose in normal brain tissue [35].

References