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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Initiation of glycogen synthesis. Control of glycogenin by glycogen phosphorylase. 840 25

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.
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PMID:Phosphorylase regulates the association of glycogen synthase with a proteoglycogen substrate in hepatocytes. 1296 9

Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been the subject of extensive investigation and much is known about its regulation by hormones such as insulin, glucagon and adrenaline (epinephrine). There has been debate over the relative importance of allosteric compared with covalent control of the key biosynthetic enzyme, glycogen synthase, as well as the relative importance of glucose entry into cells compared with glycogen synthase regulation in determining glycogen accumulation. Significant new developments in eukaryotic glycogen metabolism over the last decade or so include: (i) three-dimensional structures of the biosynthetic enzymes glycogenin and glycogen synthase, with associated implications for mechanism and control; (ii) analyses of several genetically engineered mice with altered glycogen metabolism that shed light on the mechanism of control; (iii) greater appreciation of the spatial aspects of glycogen metabolism, including more focus on the lysosomal degradation of glycogen; and (iv) glycogen phosphorylation and advances in the study of Lafora disease, which is emerging as a glycogen storage disease.
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PMID:Glycogen and its metabolism: some new developments and old themes. 2224 38