Glycogen metabolism

ATP= : adenosine triphosphate; cAMP= : cyclic adenosine monophosphate; GBE= : glycogen branching enzyme; GSK= : glycogen synthase kinase; PTG= : protein targeting to glycogen. Brain glycogen metabolism provides a typical example of metabolic coupling between neurons and astrocytes. Glycogen is almost exclusively localized in astrocytes and serves as an endogenous source of energy for these cells and for neurons. Neural activity leads to release of glutamate and other neurotransmitters that trigger mobilization of energy from glycogen in astrocytes. Glycogenolysis in astrocytes leads to the production of lactate, which serves as an energy substrate for the active neurons. Although the functional role of glycogen in the brain is incompletely understood, there is experimental evidence that glycogen is able to sustain neuronal activity during energy deprivation or in the setting of hypoxia, ischemia, hypoglycemia, or seizures. Whereas neurons also have the enzymatic machinery to synthesize glycogen, in normal conditions this process is actively inhibited, and this prevents glycogen- triggered damage of these cells. Abnormal glycogen metabolism has been typically associated with muscle disorders, but may also underlie some disorders affecting the CNS. Inability to inhibit glycogen synthesis in neurons is the basis for Lafora disease and impaired activity of glycogen branching enzyme occurs in adult polyglucosan body disease. The focus of this short review is on some physiologic aspects of brain glycogen metabolism and their clinical correlations. These topics have been comprehensively reviewed elsewhere.1–7 ### Glycogen metabolism in astrocytes. In adult brain, glycogen is predominantly present in astrocytes. Glycogen is a spherical and highly branched polymer comprising up to approximately 53,000 glycosyl units. It is synthesized from a core consisting of a peptide called glycogenin and proglycogen, which serves as a stable intermediate that is converted into macroglycogen, the storage form of glycogen.8,9 Glycogen synthesis from glucose depends on the activity of glycogen synthase, which catalyzes formation of α-1,4-glycosidic linkage of the polymer, and glycogen branching enzyme, which introduces the α-1,6-glycosidic branch points. Degradation occurs in the cytosol through …