INITIATION OF GLYCOGEN-SYNTHESIS - CONTROL OF GLYCOGENIN BY GLYCOGEN-PHOSPHORYLASE

Glycogen biosynthesis involves a specific initiation event, mediated b y a specialized protein, glycogenin. Glycogenin undergoes self-glucosy lation to generate an oligosaccharide primer, which, when long enough, supports the action of glycogen synthase to elongate the polysacchari de chain, leading ultimately to the formation of glycogen. We report t hat primed glycogenin is also a substrate for glycogen phosphorylase. Phosphorylase removed glucose from the oligosaccharide attached to gly cogenin in a phosphorolysis reaction that required phosphate and produ ced glucose 1-phosphate. The phosphorylated form, phosphorylase a, was much more effective than the dephosphorylated phosphorylase b. Howeve r, in the presence of the allosteric effector AMP, phosphorylase b als o catalyzed the phosphorolysis reaction. Glucose, an allosteric inhibi tor of phosphorylase, inhibited the reaction. Glycogen, but not a shor t oligosaccharide (maltopentaose), also inhibited the reaction. Treatm ent of fully primed glycogenin with phosphorylase converted the glycog enin to a form with slightly lower apparent molecular weight, which wa s less effective as a substrate for glycogen synthase. These results s uggest a novel role for phosphorylase in the control of glycogen biosy nthesis. We propose that the glucosylation level of glycogenin would b e determined by the balance between the self-glucosylation reaction an d the opposing action of phosphorylase. The level of glucosylation wou ld in turn determine whether or not glycogenin was an effective primer for glycogen synthase. In this way, several known controls of phospho rylase activity, such as epinephrine, glucagon, and insulin, could inf luence not only the elongation/degradation stage of glycogen metabolis m but also its initiation.