Glycogen and its Metabolism

Abstract

Glycogen is a branched polymer of glucose which serves as a reservoir of glucose units. The two largest deposits in mammals are in the liver and skeletal muscle but many cells are capable synthesizing glycogen. Its accumulation and utilization are under elaborate controls involving primarily covalent phosphorylation and allosteric ligand binding. Both muscle and liver glycogen reserves are important for whole body glucose metabolism and their replenishment is linked hormonally to nutritional status. Control differs between muscle and liver in part due to the existence of different tissue-specific isoforms at key steps. Control of synthesis is shared between transport into the muscle and the step catalyzed by glycogen synthase. Breakdown of liver glycogen, as part of blood glucose homeostasis, is also in response to nutritional cues. Muscle glycogen serves only to fuel muscular activity and its utilization is controlled by muscle contraction and by catecholamines. Though the number of enzymes directly involved in the metabolism of glycogen is quite small, many more proteins act indirectly in a regulatory capacity. Defects in the basic metabolizing enzymes lead to severe consequences whereas, with some exceptions, mutations in the regulatory proteins appear to cause a more subtle phenotypic change.

Glycogen metabolism in tissues from a mouse model of Lafora disease

“…1) is mediated by glycogen synthase, which catalyzes formation of the predominant α-1,4-glycosidic linkage of the polymer and branching enzyme, which introduces the α-1,6-glycosidic branchpoints [8]. Degradation occurs in the cytosol through the action of glycogen phosphorylase and the debranching enzyme or alternatively in the lysosome via the activity of an α-glycosidase (acid maltase or GAA).…”

Protein Degradation and Quality Control in Cells from Laforin and Malin Knockout Mice

“…Lafora disease is a non-classical type of glycogen storage disease. Glycogen is a branched storage polymer of glucose and is present in many tissues such as muscle, liver, heart, and brain (6). The synthesis of the polymer is mediated by glycogen synthase and branching enzyme and the breakdown of glycogen to glucose takes place either in the cytosol by the action of glycogen phosphorylase and debranching enzyme (AGL) 2 or in the lysosomes via ␣-acid glucosidase activity (7).…”

The role of autophagy in neonatal tissues: Just a response to amino acid starvation?

“…Glycogen can be degraded to glucose by the coordinated and sequential activity of 4 enzymes-phosphorylase, debranching enzyme, phosphoglucomutase and, in liver, glucose-6-phosphatase-or, alternatively, by the activity of a single enzyme, the lysosomal a-glucosidase, which catalyzes the hydrolysis of both a-1,4-and a-1,6-linkages in glycogen (reviewed in ref. 14). Deficiency of a-glucosidase is responsible for Pompe's disease, a glycogen storage disorder that affects especially heart and skeletal muscle and is fatal within the first year of life in patients with complete enzyme deficiency.…”

“…Finally, on should consider that the glycogen particle is a complex structure consisting of both carbohydrate and proteins (reviewed in ref. 14), thus autophagy of glycogen at birth should also lead to the degradation of the many proteins associated with glycogen particles. These include glycogenin, the self-glucosylating protein that initiates glycogen biosynthesis, protein targeting to glycogen (PTG/R5), a scaffold protein that binds both glycogen and many of the enzymes involved in glycogen metabolism, the enzymes involved in glycogen synthesis (glycogen synthase and branching enzyme) and glycogen degradation (glycogen phosphorylase, debranching enzyme), as well as regulatory enzymes, such as phosphorylase kinase, protein phosphatase-1 (PP1) and its regulatory subunits, and other components that can be recruited to glycogen particles, such as AMPK.…”