Glycogen Synthase Sensitivity to Glucose-6-P Is Important for Controlling Glycogen Accumulation in Saccharomyces cerevisiae

Bartholomew A. Pederson, Wayne A. Wilson, Peter J. Roach

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Abstract

Glycogen is a storage form of glucose utilized as an energy reserve by many organisms. Glycogen synthase, which is essential for synthesizing this glucose polymer, is regulated by both covalent phosphorylation and the concentration of glucose-6-P. With the yeast glycogen synthase Gsy2p, we recently identified two mutants, R579A/R581A/R582A and R586A/R588A/R591A, in which multiple arginine residues were mutated to alanine that were completely insensitive to activation by glucose-6-P in vitro (Pederson, B. A., Cheng, C., Wilson, W. A., and Roach, P. J. (2000) J. Biol. Chem. 275, 27753-27761). We report here the expression of these mutants in Saccharomyces cerevisiae and, as expected from our findings in vitro, they were not activated by glucose-6-P. The R579A/R581A/R582A mutant, which is also resistant to inhibition by phosphorylation, caused hyperaccumulation of glycogen. In contrast, the mutant R586A/R588A/R591A, which retains the ability to be inactivated by phosphorylation, resulted in lower glycogen accumulation when compared with wild-type cells. When intracellular glucose-6-P levels were increased by mutating the PFK2 gene, glycogen storage due to the wild-type enzyme was increased, whereas that associated with R579A/R581A/R582A was not greatly changed. This is the first direct demonstration that activation of glycogen synthase by glucose-6-P in vivo is necessary for normal glycogen accumulation.

Original languageEnglish (US)
Pages (from-to)13764-13768
Number of pages5
JournalJournal of Biological Chemistry
Volume279
Issue number14
DOIs
StatePublished - Apr 2 2004

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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