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.