Alkylglycosides as artificial primers for glycogen biosynthesis

Glycogenin is a 37 kDa self-glycosylating protein which has been demonstrated to be the initiating enzyme and primer for glycogen biosynthesis in liver, skeletal muscle and other tissues. We have recently shown that glycogenin will use alkylglucosides and alkylmaltosides as artificial acceptors in glycosyl transfer from UDP-glucose and UDP-xylose in vitro and have suggested that such substrates might be used to promote the synthesis of glycogen in vitro and in vivo. We now report that alkylglycosides can also serve as acceptors 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 alkylmaltosides were preferred over alkylglucosides. The hydrophobicity of the substrates markedly affected their acceptor activity, less hydrophobic substrates being more active. This is in contrast to the behavior of glycogenin, which acted preferentially upon the more hydrophobic substrates tested. Aromatic glycosides were also substrates for glycogen synthase, e.g., naphthyl-alpha-D- and beta-D-glucoside. The substrates were active in vitro both with partially purified rabbit muscle glycogen synthase 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 uptake of 14C-glucose in liver. The elevated uptake was due to an increase in both hydrophobic products, isolated by adsorption to Sep-Pak C18 columns, and more hydrophilic material that co-fractionated with glycogen upon treatment of the tissue with alkali and precipitation with ethanol. These results demonstrate the ability of alkylglycosides to serve as artificial primers for glycogen biosynthesis in vivo.