Glycogen and its metabolism: some new developments and old themes

Abstract

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.

Attenuation of Armanni–Ebstein lesions in a rat model of diabetes by a new anti-fibrotic, anti-inflammatory agent, FT011

“…New glycogen particles are initiated by the enzyme glycogenin, which covalently attaches a chain of glucose residues to a specific amino acid within its polypeptide chain [4]. Thus the 140-fold increase in glycogenin protein production we find in the diabetic rat correlates to a 140-fold increase in the number of glycogen particles.…”

“…The new glycogen particle is further elongated by the activities of glycogen synthase and glycogen-branching enzyme. Glycogen synthase activity is increased in the diabetic kidney, which may be caused by either protein phosphatase-mediated dephosphorylation (leading to active glycogen synthase) or allosteric activation by glucose-6-phosphate (G6P) [4]. We hypothesise that the latter is most likely due to high intracellular G6P concentrations formed by the action of glucokinase in response to the high intracellular glucose concentration (data not shown).…”

“…1d) activities. Kidney lysates were incubated with α-amylase, an enzyme that digests the glycogen particle and exposes glycogenin found at the glycogen core [4], and assessed for glycogenin levels via western blotting. Protein levels of glycogenin were found to be 140-fold higher (Fig.…”

“…We hypothesise that the latter is most likely due to high intracellular G6P concentrations formed by the action of glucokinase in response to the high intracellular glucose concentration (data not shown). High G6P would also explain the reduced glycogen phosphorylase activity in the diabetic kidneys, since G6P allosterically inhibits glycogen phosphorylase [4].…”

“…Glycogen consists of a core protein, glycogenin, with covalent α-1,4-glycosidic linkages attached to the polypeptide chain that are extended by the collaborative actions of glycogen synthase and glycogen-branching enzyme. Glycogen degradation is mediated by the concerted action of glycogen phosphorylase and glycogen-debranching enzyme [4].…”