Initiation of glycogen synthesis. Control of glycogenin by glycogen phosphorylase

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21 Scopus citations

Abstract

Glycogen biosynthesis involves a specific initiation event, mediated by a specialized protein, glycogenin. Glycogenin undergoes self-glucosylation to generate an oligosaccharide primer, which, when long enough, supports the action of glycogen synthase to elongate the polysaccharide chain, leading ultimately to the formation of glycogen. We report that primed glycogenin is also a substrate for glycogen phosphorylase. Phosphorylase removed glucose from the oligosaccharide attached to glycogenin in a phosphorolysis reaction that required phosphate and produced glucose 1-phosphate. The phosphorylated form, phosphorylase a, was much more effective than the dephosphorylated phosphorylase b. However, in the presence of the allosteric effector AMP, phosphorylase b also catalyzed the phosphorolysis reaction. Glucose, an allosteric inhibitor of phosphorylase, inhibited the reaction. Glycogen, but not a short oligosaccharide (maltopentaose), also inhibited the reaction. Treatment of fully primed glycogenin with phosphorylase converted the glycogenin to a form with slightly lower apparent molecular weight, which was less effective as a substrate for glycogen synthase. These results suggest a novel role for phosphorylase in the control of glycogen biosynthesis. We propose that the glucosylation level of glycogenin would be determined by the balance between the self-glucosylation reaction and the opposing action of phosphorylase. The level of glucosylation would in turn determine whether or not glycogenin was an effective primer for glycogen synthase. In this way, several known controls of phosphorylase activity, such as epinephrine, glucagon, and insulin, could influence not only the elongation/degradation stage of glycogen metabolism but also its initiation.

Original languageEnglish (US)
Pages (from-to)21717-21721
Number of pages5
JournalJournal of Biological Chemistry
Volume268
Issue number29
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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