Biomedical Sciences –Metabolism 5
Glycogen Metabolism: Breakdown and Control
Glycogen is the main storage form of glucose in animals, especially abundant in the liver and
muscle tissues. It consists of glucose units linked primarily by alpha-1,4 glycosidic bonds,
with branches connected by alpha-1,6 linkages. This branched structure increases solubility
and provides many terminal ends for rapid mobilization.
When the body requires glucose, glycogen phosphorylase catalyzes the removal of glucose
units from glycogen by breaking the alpha-1,4 bonds, releasing glucose-1-phosphate (G1P).
Using inorganic phosphate rather than water prevents free glucose release, keeping glucose
inside the cell for metabolism.
Phosphoglucomutase then converts G1P into glucose-6-phosphate (G6P), which enters
glycolysis for energy production in muscle cells. In liver cells, G6P can be dephosphorylated
by glucose-6-phosphatase to free glucose for release into the bloodstream, helping maintain
blood sugar levels.
At branch points, debranching enzymes transfer glucose residues and hydrolyze alpha-1,6
linkages to allow glycogen phosphorylase to continue its action.
Regulation is tightly controlled by hormones. Glucagon and epinephrine trigger signaling
cascades raising cAMP levels, activating protein kinase A (PKA), which phosphorylates
phosphorylase kinase and subsequently glycogen phosphorylase, enhancing glycogen
breakdown.
Conversely, insulin promotes the dephosphorylation of these enzymes, inhibiting
glycogenolysis during fed states.
Glycogen Synthesis and Its Regulation
Glycogen synthesis starts with glucose-6-phosphate being converted to glucose-1-
phosphate, then activated to UDP-glucose (UDPG), which serves as the glucose donor for
glycogen chain elongation.
Glycogen synthase catalyzes the formation of alpha-1,4 glycosidic bonds, extending the
glycogen chain. However, glycogen synthase requires a primer, provided by the protein
glycogenin, which autoglycosylates itself to form the initial glucose chain.
Branching enzymes create alpha-1,6 linkages that form branch points, increasing glycogen’s
solubility and providing multiple ends for rapid synthesis and degradation.
Glycogen synthase is active when dephosphorylated (stimulated by insulin) and inactive
when phosphorylated (stimulated by glucagon and epinephrine), allowing tight hormonal
regulation of glycogen storage.
Glycogen Metabolism: Breakdown and Control
Glycogen is the main storage form of glucose in animals, especially abundant in the liver and
muscle tissues. It consists of glucose units linked primarily by alpha-1,4 glycosidic bonds,
with branches connected by alpha-1,6 linkages. This branched structure increases solubility
and provides many terminal ends for rapid mobilization.
When the body requires glucose, glycogen phosphorylase catalyzes the removal of glucose
units from glycogen by breaking the alpha-1,4 bonds, releasing glucose-1-phosphate (G1P).
Using inorganic phosphate rather than water prevents free glucose release, keeping glucose
inside the cell for metabolism.
Phosphoglucomutase then converts G1P into glucose-6-phosphate (G6P), which enters
glycolysis for energy production in muscle cells. In liver cells, G6P can be dephosphorylated
by glucose-6-phosphatase to free glucose for release into the bloodstream, helping maintain
blood sugar levels.
At branch points, debranching enzymes transfer glucose residues and hydrolyze alpha-1,6
linkages to allow glycogen phosphorylase to continue its action.
Regulation is tightly controlled by hormones. Glucagon and epinephrine trigger signaling
cascades raising cAMP levels, activating protein kinase A (PKA), which phosphorylates
phosphorylase kinase and subsequently glycogen phosphorylase, enhancing glycogen
breakdown.
Conversely, insulin promotes the dephosphorylation of these enzymes, inhibiting
glycogenolysis during fed states.
Glycogen Synthesis and Its Regulation
Glycogen synthesis starts with glucose-6-phosphate being converted to glucose-1-
phosphate, then activated to UDP-glucose (UDPG), which serves as the glucose donor for
glycogen chain elongation.
Glycogen synthase catalyzes the formation of alpha-1,4 glycosidic bonds, extending the
glycogen chain. However, glycogen synthase requires a primer, provided by the protein
glycogenin, which autoglycosylates itself to form the initial glucose chain.
Branching enzymes create alpha-1,6 linkages that form branch points, increasing glycogen’s
solubility and providing multiple ends for rapid synthesis and degradation.
Glycogen synthase is active when dephosphorylated (stimulated by insulin) and inactive
when phosphorylated (stimulated by glucagon and epinephrine), allowing tight hormonal
regulation of glycogen storage.
