Glycogenesis

• Glycogen is a glucose store in cells.
• The structure of Glycogen is a highly branched (1,4) - glucose polymer.
• Glucagon receptor is not present on myocytes.
• Glycogen storage disease is a generic term that describes a group of inherited disorders characterized by deposition of an abnormal type or quantity of glycogen in the tissues.
• Glycogenesis is when Glc is incorporated into glycogen in the liver and muscle.
• Glycogenolysis is when Glucose is mobilized from glycogen in the liver and muscle.
• Hormonal regulation of hepatic glycogenesis and glycogenolysis is done by insulin and glucagon.
• Insulin and glucagon signal through phosphorylations and pathway flips.
• Glycogenolysis in the liver is used for plasma glycemia maintenance, both acute and postabsorptive.
• Glycogenolysis in muscle is used for mobilizing glucose for ATP contraction activity.
• Glycogenesis is regulated to replenish glycogen stores or meet immediate needs.
• Inborn errors of metabolism include glycogen storage diseases.
• High blood glucose levels indicate a fed state, where insulin stimulates glycogen synthesis and inhibits glycogen breakdown.
• Glucagon is used in a starved state, where it stimulates glycogen breakdown and inhibits glycogen synthesis.
• Blood glucose can be obtained from three primary sources: diet, gluconeogenesis, and degradation of glycogen.
• Red blood cells and the brain have an absolute requirement for blood glucose for their energy metabolism, consuming about 80% of the glucose consumed per day by a 70 kg human, in good health.
• Blood and extracellular fluid volume contains about 10 - 30 g glucose, which must be replenished constantly.
• Glycogen is a homopolysaccharide composed of only glucose residues designed as a branched chain.
• Glycogen metabolism requires the addition of glucose to the non-reducing ends of glycogen via UDP-glucose.
• The α-1,4-linkage predominates the whole molecule, with branches taking place in every 6 - 10 residues with α-1,6-linkage.
• Inside the cell, glucose is phosphorylated to glucose-6-phosphate, catalyzed by hexokinase in muscle and glucokinase in liver.
• Glycogen synthesis and degradation utilize separate pathways (enzymes).
• UDP glucose is the activated form of glucose.
• UDP-glucose pyrophosphorylase: Glucose 1-phosphate + UTP → UDP-glucose + PPi.
• Glycogenin catalyzes the transfer of the next few molecules of glucose from UDP-glucose, producing a short, α(1→4) - linked glucosyl chain.
• Pyrophosphate (PPi), is hydrolyzed to two inorganic phosphates (Pi) by pyrophosphatase, ensuring that the UDP-glucose pyrophosphorylase reaction proceeds in the direction of UDP-glucose production.
• Luis Leloir and his coworkers showed that glycogen is synthesized by a pathway that utilizes uridine diphosphate glucose (UDP-glucose) rather than glucose 1-phosphate as the activated glucose donor.
• Activated glucosyl unit of UDP-glucose is transferred to the hydroxyl group at a C-4 terminus of glycogen to form an alpha 1-4 glycosidic bond
• Once glucose 1-Phosphate is formed, it needs to be activated by adding another phosphoryl group and a uridine molecule to form uridine diphosphate (UDP) - glucose.
• Glucose-6-phosphate is isomerized to glucose-1-phosphate by phosphoglucomutase.
• In the cytosol of hepatocyte and myocyte, glycogenin can serve as an acceptor of glucose residues from UDP-glucose.
• Luis Leloir won the Nobel Prize in Chemistry in 1970 for his discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates.
• Although the reaction is reversible, the hydrolysis of the pyrophosphate pushes it to the right.
• The side chain hydroxyl group of a specific tyrosine serves as the site at which the initial glucosyl unit is attached.
• Glucose 1,6-bis phosphate is an obligatory intermediate in this reaction.
• Glycogen synthase is responsible for making the α(1→4) linkages in glycogen.
• The reaction is catalyzed by glycogenin itself via autoglycosylation; glycogenin is an enzyme.
• High blood glucose levels indicate a fed state, stimulating glycogen synthesis and inhibiting glycogen breakdown.
• Unlike hepatocytes, myocytes have a reserve of GLUT4 sequestered in intracellular vesicles, and insulin triggers their movement to the plasma membrane, where they allow increased glucose uptake.
• Glucagon, secreted during a fast, stimulates glycogen breakdown and inhibits glycogen synthesis.