ALKYLGLYCOSIDES AS ARTIFICIAL PRIMERS FOR GLYCOGEN BIOSYNTHESIS

Glycogenin is a 37 kDa self-glycosylating protein which has been demon strated to be the initiating enzyme and primer for glycogen biosynthes is in liver, skeletal muscle and other tissues. We have recently shown that glycogenin will use alkylglucosides and alkylmaltosides as artif icial accepters in glycosyl transfer from UDP-glucose and UDP-xylose i n vitro and have suggested that such substrates might be used to promo te the synthesis of glycogen in vitro and in vivo. We now report that alkylglycosides can also serve as accepters for transfer of glucose by glycogen synthase, yielding alkylmaltooligosaccharide products which may potentially be elongated to glycogen. alpha-Glucosides were better substrates than the corresponding beta-glucosides, and alkylmaltoside s were preferred over alkylglucosides. The hydrophobicity of the subst rates markedly affected their acceptor activity, less hydrophobic subs trates being more active. This is in contrast to the behavior of glyco genin, which acted preferentially upon the more hydrophobic substrates tested. Aromatic glycosides were also substrates for glycogen synthas e, e.g., naphthyl-alpha-D- and beta-D-glucoside. The substrates were a ctive in vitro both with partially purified rabbit muscle glycogen syn thase and in incubations with crude muscle and liver homogenates from rat. In vivo experiments with mice further proved that intraperitoneal administration of alkylglucosides and alkylmaltosides increased the u ptake of C-14-glucose in liver. The elevated uptake was due to an incr ease in both hydrophobic products, isolated by adsorption to Sep-Pak C -18 columns, and more hydrophilic material that co-fractionated with g lycogen upon treatment of the tissue with alkali and precipitation wit h ethanol. These results demonstrate the ability of alkylglycosides to serve as artificial primers for glycogen biosynthesis in vivo.