Glycogen Metabolism I PDF

Glycogen Metabolism I ILOs: 1. Define structure and types of glycogen. 2. Describe the nature, functions of glycogenesis. 3. Mention differences between glycogenesis and glycogenlysis. 4. Explain regulation of glycogenesis and glycogenlysis. I. Structure of glycogen: A. Glycogen is h...

Glycogen Metabolism I ILOs: 1. Define structure and types of glycogen. 2. Describe the nature, functions of glycogenesis. 3. Mention differences between glycogenesis and glycogenlysis. 4. Explain regulation of glycogenesis and glycogenlysis. I. Structure of glycogen: A. Glycogen is homopolysaccharide formed of branched α D glucose units (α 1,4 and α 1,6). B. The main glycosidic bond is α1-4-linkage. Only at the branching point, the chain is attached by α1-6 linkage. C. Each branch is made of 12-14 glucose units. II. Location of glycogen: Glycogen is present mainly in cytosol of liver and muscles. A. Liver glycogen is about 120 grams (about 6% of liver weight). B. Muscle glycogen is about 350 grams (about 1% of total muscles weight). III. Functions of glycogen: A. Liver glycogen: It maintains normal blood glucose concentration especially during the early stage of fast (between meals). After 12-18 hours fasting, liver glycogen is depleted. B. Muscle glycogen: It acts as a source of energy within the muscle itself especially during muscle contractions. IV. Synthesis of glycogen (glycogenesis): A. Definition: It is the formation of glycogen in liver and muscles. B. Substrates for glycogen synthesis: 1. In liver: a) Blood glucose. b) Other hexoses: fructose and galactose. c) Non-carbohydrate sources: (gluconeogenesis) e.g. glycerol and lactate. These are converted first to glucose, then to glycogen. 2. In muscles: a) Blood glucose only. C. Steps: Glucose molecules are the first activated to uridine diphosphateglucose (UDP-G). Then these UDP-G molecules are added to a glycogen primer to form glycogen. 1. Formation of UDP-Glucose (UDP-G): NB: Glucose is converted into glucose-6-phosphate by glucokinase in liver and hexokinase in muscles. 2. Formation of glycogen: a) UDP-Glucose reacts with glycogen primer, which may be: 1) Few molecules of glucose linked together by α1-4 linkage. 2) A protein called glycogenin. UDP-G molecules react with -OH of tyrosine of that protein to initiate glycogen synthesis. b) Glycogen synthase enzyme: By the action of glycogen synthase (key enzyme of glycogenesis), UDP-G molecules are added to glycogen primer causing elongation of the α1-4 branches up to 12-14glucose units.  c) Branching enzyme: It transfers parts of the elongated chains (5-8 glucose residues) to the next chain forming a new αI-6 glycosidic bond. The new branches are elongated by the glycogen synthase and the process is repeated. V. Breakdown of glycogen (Glycogenolysis): A. Definition: - It is the breakdown of glycogen into glucose (in liver) and lactic acid (in muscles). - The degradative pathway that mobilizes stored glycogen in liver and skeletal muscle is not a reversal of the synthetic reactions. A separate set of cytosolic enzymes is required. - When glycogen is degraded, the primary product is glucose 1- phosphate, obtained by breaking α(1→4) glycosidic bonds. In addition, free glucose is released from each α(1→6)-linked glucosyl residue. B. Steps: 1. Glycogen phosphorylase (the key enzyme of glycogenolysis): - acts on α1-4 bonds, breaking it down by phosphorolysis (i.e. breaking down by addition of inorganic phosphate "Pi"). - Therefore, it removes glucose units in the form of glucose-1- phosphate. - Phosphorylase enzyme acts on the branches containing more than 4 glucosyl units. 2. transferase enzyme: - When the branch contains 4 glucose units, 3 of them are transferred to a next branch by transferase enzyme, leaving the last one. 3. debranching enzyme: - The last glucose unit that is attached to the original branch by α 1-6 bond is removed by debranching enzyme by hydrolysis (i.e. breaking the bond down by addition of H 2O).  4. Glucose-1-phosphate molecules are converted to glucose-6-phosphate, by mutase enzyme. Fate of glucose-6-phosphate: a) In liver: glucose-6-phosphate is converted to free glucose by glucose-6-phosphatase. b) In muscles: there is no glucose-6-phosphatase, so glucose-6- phosphate enters glycolysis to give lactate. Lysosomal degradation of glycogen A small amount (1–3%) of glycogen is continuously degraded by the lysosomal enzyme, α (1→4)-glucosidase (acid maltase). The purpose of this pathway is unknown. However, a deficiency of this enzyme causes accumulation of glycogen in vacuoles in the lysosomes, resulting in the serious glycogen storage disease Type II: Pompe disease. VI. Differences between liver glycogen and muscle glycogen: Liver glycogen Muscle glycogen Sources: 1- Blood glucose. Blood glucose only. 2- other hexoses: e.g. fructose. 3- Non-carbohydrate sources: e.g. lactate Amount: 120 grams maximum 350 gram maximum Concentration: 6% 1% Functions: It maintains normal blood private source of energy for glucose concentration muscles only between meals End-product: Glucose Lactate (due to absence ofglucose-6- phosphatase). Effect of hormone: Insulin: Stimulates glycogenesis Same Epinephrine: Stimulates glycogenolysis Same Glucagon: Stimulates glycogenolysis No effect