Glycogenesis 1

• Glycogen is a glucose store in cells.
• The structure of Glycogen is a highly branched (1,4) - glucose polymer.
• 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.
• PIP 2 ® DAG +IP 3 , 2 nd messengers.
• DAG activates PKC (like PKA), leading to activation of glycogen phosphorylase and glucose release to blood.
• Insulin’s two main functions are to lower blood glucose by reversing the effect of glucagon’s phosphorylation of enzymes and proteins, and to stimulate gene expression of carbohydrate metabolism enzymes.
• b-adrenergic receptor (cAMP) activates glycogenolysis for fight or flight, prolonged exercise, and two hormone independent modes: Influx of Ca 2+ activates phosphorylase kinase via Ca 2+ – calmodulin complex, and AMP activates phosphorylase directly.
• Epinephrine response: augments glucagon’s during severe hypoglycemia, causing symptoms such as rapid heartbeat, sweating, tremors and anxiety.
• a-receptor: G-proteins, active membrane isozyme of phospholipase C (PLC): specific for cleavage of membrane phospholipid (PL), and PIP 2.
• Muscle lacks glucagon receptor and G6Phosphatase enzyme.
• Muscle reacts to epinephrine not glucagon.
• 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.
• Normally, blood glucose range is between 70 – 100 mg/dL, indicating normoglycemia.
• Few hormone molecules binding to their receptors result in a number of PKA molecules being activated.
• Glycogen phosphorylase uses pyridoxal phosphate (PLP), a derivative of pyridixine (vitamin B6), as a coenzyme.
• B6 is required for the mobilization of glucose from glycogen.
• In skeletal muscle, glycogenolysis occurs during active exercise, and glycogenesis begins as soon as the muscle is again at rest.
• B6 is also required for other biochemical reactions such as transamination.
• The critical Pi substrate is bound to the active site by interactions with pyridoxal phosphate (PLP) and active site amino acids.
• Glycogen Phosphorylase exists in two different forms: Glycogen Phosphorylase a (Active Form, Phosphorylated) and Glycogen Phosphorylase b (Inactive Form).
• The phosphorylation event takes place in glycogen phosphorylase when hormones, such as glucagon or epinephrine, bind to plasma membrane G protein-coupled receptors.
• Glycogen phosphorylase is one of the first enzymes shown to be controlled by reversible phosphorylation.
• PKA can each activate many phosphorylase kinase molecules.
• Activation of glycogen degradation by cAMP-directed pathway is a sequential process with many steps to amplify the effect of the hormonal signal.
• The pathways of glycogen synthesis and degradation are allosterically controlled to meet the needs of a particular tissue.
• Glycogen synthase and glycogen phosphorylase are hormonally regulated to meet the needs of the body as a whole.
• In the liver, glycogenesis accelerates during periods when the body has been well fed, whereas glycogenolysis accelerates during periods of fasting.
• The synthesis and degradation of glycogen are tightly regulated due to the importance of maintaining blood glucose levels.
• Glycogen is a homopolysaccharide composed of only glucose residues designed as a branched chain.