Manganese sulfate-dependent glycosylation of endogenous glycoproteins in human skeletal muscle is catalyzed by a nonglucose 6-P-dependent glycogen synthase and not glycogenin

Glycogenin, a Mn2+-dependent, self-glucosylating protein, is considered to catalyze the initial glucosyl transfer steps in glycogen biogenesis. To stu dy the physiologic significance of this enzyme, measurements of glycogenin mediated glucose transfer to endogenous trichloroacetic acid precipitable m aterial (protein-bound glycogen, i.e., glycoproteins) in human skeletal mus cle were attempted. Although glycogenin protein was detected in muscle extr acts, activity was not, even after exercise that resulted in marked glycoge n depletion. Instead, a MnSO4-dependent glucose transfer to glycoproteins, inhibited by glycogen and UDP-pyridoxal (which do not affect glycogenin), a nd unaffected by CDP (a potent inhibitor of glycogenin), was consistently d etected. MnSO4-dependent activity increased in concert with glycogen syntha se fractional activity after prolonged exercise, and the MnSO4-dependent en zyme stimulated glucosylation of glycoproteins with molecular masses lower than those glucosylated by glucose 6-P-dependent glycogen synthase. Additio n of purified glucose 6-P-dependent glycogen synthase to the muscle extract did not affect MnSO4-dependent glucose transfer, whereas glycogen synthase antibody completely abolished MnSO4-dependent activity. It is concluded th at: (1) MnSO4-dependent glucose transfer to glycoproteins is catalyzed by a nonglucose 6-P-dependent form of glycogen synthase; (2) MnSO4-dependent gl ycogen synthase has a greater affinity for low molecular mass glycoproteins and may thus play a more important role than glucose 6-P-dependent glycoge n synthase in the initial stages of glycogen biogenesis; and (3) glycogenin is generally inactive in human muscle in vivo. (C) 1999 Elsevier Science B .V, All rights reserved.