Inhibition of brain protein fucosylation by sulfated sugar molecules.
Brain fucosyltransferase reaction (GDP-fucose: glycoprotein fucosyltransferase, EC 2.4.1.68) was found to be inhibited by heparin. Also a variety of other sulfated polysaccharides led to a decrease in the fucosyltransferase reaction comparable to that induced by heparin. This action seems not to be related to the structural and functional integrity of the glucosaminoglycan since the same effect of the enzyme reaction was seen using its breakdown products obtained by hydrolysis or ultrasonics. In contrast, unsulfated polysaccharides and constituents of heparin, respectively, did not influence the enzyme reaction at all. The same was true for phosphorylated monosaccharides. Therefore, it seems likely that the inhibitory effect of appropriate polysaccharides or their breakdown products is related to the action of sulfated sugar units. Moreover, investigating the influence of a heparin hydrolysate on the incorporation of [3H]fucose into the glycoproteins of hippocampal slices, also an inhibition of the sugar incorporation was found. Thus, the inhibitory influence of sulfated sugar units on brain fucosyltransferase reaction seems to be effective under both conditions, in the assay system of the enzyme in vitro as well as in intact cells of the hippocampal structure.
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D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005944:Glucosamine / Q000494:pharmacology; D005965:Glucuronates / Q000494:pharmacology; D020723:Glucuronic Acid; D006493:Heparin / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014465:Ultrasonics
D003911:Dextrans; D005965:Glucuronates; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D011479:Protamines; D005643:Fucose; D020723:Glucuronic Acid; D006493:Heparin; D016264:Dextran Sulfate; D005647:Fucosyltransferases; D005944:Glucosamine