title: Phosphorylase regulates the association of glycogen synthase with a proteoglycogen substrate in hepatocytes.
abstract: Changes in the glucosylation state of the glycogen primer, glycogenin, or its association with glycogen synthase are potential sites for regulation of glycogen synthesis. In this study we found no evidence for hormonal control of the glucosylation state of glycogenin in hepatocytes. However, using a modified glycogen synthase assay that separates the product into acid-soluble (glycogen) and acid-insoluble (proteoglycogen) fractions we found that insulin and glucagon increase and decrease, respectively, the association of glycogen synthase with an acid-insoluble substrate. The latter fraction had a higher affinity for UDP-glucose and accounted for between 5 and 21% of total activity depending on hormonal conditions. Phosphorylase overexpression mimicked the effect of glucagon. It is concluded that phosphorylase activation or overexpression causes dissociation of glycogen synthase from proteoglycogen causing inhibition of initiation of glycogen synthesis.
authors.affiliation: School of Clinical Medical Sciences-Diabetes, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Tavridou
authors.forename: Loranne
authors.initials: L
authors.lastname: Agius
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005934:Glucagon / Q000502:physiology; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005964:Glucosyltransferases; D006003:Glycogen / Q000096:biosynthesis* / Q000737:chemistry; D024981:Glycogen Phosphorylase / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014238:Trichloroacetic Acid / Q000737:chemistry; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
chemical_list: D006023:Glycoproteins; C051887:glycogenin; D008345:Manganese; D019298:Glucose-6-Phosphate; D014238:Trichloroacetic Acid; D006003:Glycogen; D005934:Glucagon; D005964:Glucosyltransferases; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D014532:Uridine Diphosphate Glucose