NUTR 470 1st Edition Lecture 9-Glycogen Metabolism• Glycogenolysis: -The breakdown of glycogen-Glycogenolysis is not the reverse of glycogenesis, but a separate pathway.-Glucose is removed from glycogen in an active and phosphorylated form – glucose-1-phosphate.-Glucose-1-phosphate is converted to glucose-6-phosphate.-Glycogen phosphorylase catalyzes the reaction to remove glucose residues from glycogen.• branching-Glycogen phosphorylase cannot remove glucose residues from the branch points (a-1,6 linkages) in glycogen.-Debranching enzyme firstly transfers three glucose subunits.-Debranching enzyme then cuts the remaining residue at the a 1 → 6 linkage.-Glycogen phosphorylase removes glucose residues in a 1→4 linkages.• The fate of glucose-6-phosphate-In the liver— • Glucose-6-phosphate is hydrolyzed to glucose by glucose-6-phosphatase.• This is the function of the phosphatase-In muscle—• Glucose-6-phosphate is oxidized in the glycolytic pathway.• They have different functions• this is the way to save glucose under fasting conditions-Glycogenolysis and Glucose Homeostasis• Glycogenolysis is crucial for the control of glucose homeostasis.-Glycogenolysis in the liver• Glycogenolysis, along with gluconeogenesis, is responsible for glucose production from the liver.• responds to signals, and signal cascade lead to activity-Estimation of endogenous glucose production• Glycogenolysis, together with gluconeogenesis, is used to estimate the endogenous glucose production.• another pathway for glucose productionDephosphorylation-1) glycolysis-2) PDH-3) GS-4) GP-5)HSL-take the phosphate away and make the enzymes-fasting conditions… glucagon… signal cascades-transferase-covalent activation--Regulation of Glycogenolysis-Glycogen phosphorylase is the enzyme that catalyzes the rate-determining step in glycogenolysis. • Covalent activation-cAMP, at high levels, activates cAMP-dependent protein kinase.-cAMP-dependent protein kinase phosphorylates and activates glycogen phosphophorylase.-Regulation of Glycogenolysis• Effects of hormones• Glucagon and epineprine are hormones that stimulate glycogenolysis.• Glucagon or epineprine, through signaling transduction, causes an increase in the levels of cAMP.• increase of cAMP—increases Glycogenolysis-Regulation of cAMP• Upon binding a receptor, epinephrine causes an increase in the levels of cAMP.• adrenaline— function is very similar-Regulation of Glycogenolysis• Effects of hormones-Insulin, through signaling transduction, causes a decrease in the levels of cAMP.-Insulin, working together withglucose, is a hormone that suppresses glycogenolysis.-decrease in cAMP — decreases Glycogenolysis-Cooperative Regulation of Glycogenolysis• When glucose levels are high: increase of insulin; decrease on glucagon— results in decreased glycogenolysis• When glucose levels are low: Decrease of insulin; increase on glucagon— results in increase glycogenolysis-Coordination in Glycogenolysis and Glycogenesis• Insulin/reduced levels of glucagon and epinephrine-De-phosphorylating and inactivating glycogen phosphorylase-De-phosphorylating and activating glycogen synthase-decrease Glycogenolysis— increase Glycogenesis-Coordination in Glycogenolysis and Glycogenesis• Glucagon and epineprine-Phosphorylating and activating glycogen phosphorylase-Phosphorylating and inactivating glycogen synthase• increase of Glycogenolysis— decreases Glycogenesis-Coordination in Glycogenolysis and Glycogenesis• When glucose levels are high-increase of Insulin and decrease ofGlucagon —>decrease of glycogenolysis-decrease of Insulin and increase ofGlucagon —> increase of glycogenolysis• Promoting glucose storage• When glucose levels are low-decrease of Insulin and increase ofGlucagon —> increase of glycogenolysis-decrease of Insulin and increase ofGlucagon —> increase of glycogenesis• Promoting glucose production from the liver- Key points for coordination• When glucose is in excess, there should be an increase in glucose storage (glycogenesis).• When glucose is not enough, there should be an increase in glycogenolysis in the liver to export glucose.• Glucose, at high levels, stimulates the secretion of insulin and inhibits the secretion of glucagon.• Stress and emerging reactions (sympathetic excitement) stimulate the secretion of epinephrine.• Conditions when glucose is needed!-Coordination in Glycogenolysis and Gluconeogenesis-When glucose levels are high• increase Insulin, decrease Glucagon—> decreases Glycogenolysis• increase of Insulin, decreases Glucagon —> decrease in Gluconeogenesis-Rapid regulation of glucose homeostasis.-When glucose levels are low• decrease Insulin, increases Glucagon—> increases Glycogenolysis• decrease of Insulin, increases Glucagon —> increases in Gluconeogenesis-Rapid regulation of glucose homeostasis.-Disease Related to Glycogen Metabolism• Glycogen storage disease-GSD results from enzyme defects that affect the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types.-GSD is a group of inherited disorders.-Symptoms include enlarged liver, low blood sugar, growth retardation, and an abnormal blood chemistry. Each type of GSD also has its own specific symptoms.-Definitive diagnosis—-Based only on a biopsy of the affected organ.-Dietary treatment— • A well-controlled diet to ensure consistent levels of blood glucose.-Summary• Reactions of glycogenolysis• Coordination in glycogen metabolism• Glycogen phosphorylase• Glycogen storage disease• Regulation of