Inhibition of hyaluronate synthesis.
UDP-GlcNAc (UDP-N-acetylglucosamine) and UDP-GlcA (UDP-glucuronic acid) were oxidized by periodate in the ribose ring and utilized as inhibitors for hyaluronate synthase in membrane fractions from the B6 cell line and in cell cultures of B6 cells and human fibrosarcoma HT 1080. Inhibition was irreversible and concentration-dependent and could be prevented in the case of periodate-oxidized UDP-GlcNAc by UDP-GlcNAc. Periodate-oxidized UDP-GlcNAc was shown to block chain elongation of hyaluronate. Introduction of periodate-oxidized UDP-GlcA into B6 cells by hypo-osmotic lysis of pinocytotic vesicles decreased hyaluronate synthesis by direct inhibition of the synthase. In HT 1080 cells the synthesis of hyaluronate, chondroitin sulphate and heparan sulphate was inhibited simultaneously.
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D002460:Cell Line; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors; D006025:Glycosaminoglycans / Q000096:biosynthesis; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007700:Kinetics; D008565:Membrane Proteins; D010504:Periodic Acid; D014166:Transferases; D014535:Uridine Diphosphate Glucuronic Acid / Q000494:pharmacology*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000494:pharmacology*; D014539:Uridine Diphosphate Sugars / Q000494:pharmacology*; D029867:Xenopus Proteins
D006025:Glycosaminoglycans; D008565:Membrane Proteins; D014539:Uridine Diphosphate Sugars; D029867:Xenopus Proteins; D010504:Periodic Acid; D014535:Uridine Diphosphate Glucuronic Acid; D014537:Uridine Diphosphate N-Acetylglucosamine; D006820:Hyaluronic Acid; C009288:metaperiodate; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases