Lecture 21 (Glycogen Metabolism) PDF

Lippincott’s illustrated reviews Chapter 11 – Page 125 Lecture 21 Glycogen Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Differentiate between the function of liver and muscle glycogen. Discuss glycogenesis and...

Lippincott’s illustrated reviews Chapter 11 – Page 125 Lecture 21 Glycogen Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Differentiate between the function of liver and muscle glycogen. Discuss glycogenesis and glycogenolysis processes. Understand hormonal regulation of glycogen metabolism. Explain the reason for glycogen storage disease type I and II. 2 3  Structure and Function of Glycogen The main stores of glycogen in the body are found in skeletal muscle and liver, although most of other cells store small amounts of glycogen for their own use. The function of muscle glycogen is to serve as a fuel reserve for synthesis of adenosine triphosphate (ATP) during muscle contraction. That of liver glycogen is to maintain the blood glucose concentration, particularly during the early stages of a fast. 4  A. Amount of liver and muscle glycogen Approximately 400 g of glycogen make up 1-2% of the fresh weight of resting muscle, and approximaetly 100g of glycogen make up to 10% of the fresh weight of well-fed adult liver. 5  B. Glycogen Structure 6  Synthesis of Glycogen (Glycogenesis) Glycogen is synthesized from molecules of α-D-glucose which convert to UDP-glucose as active form of glucose to start glycogenesis process. The process occurs in the cytosol, and requires energy supplied by ATP. Glycogen synthase is responsible for making the α(1→4) linkages in glycogen. Branches are made by the action of the branching enzyme, amylo-α(1→6)-transglucosidase. 7 8  Degradation of glycogen (Glycogenolysis) down of glycogen A. Shortening of chains Breaking 7 synthse Glycogen phosphorylase sequentially cleaves α(1→4) glycosidic bond at the non-reducing ends of the glycogen chain producing glucose-1-phosphate. 9 10 11 B. Removal of branches Branches are removed by the two debranching enzyme. First, α(1→4)-glucan transferase activity removes the outer three of the four glucosyl residues attached at a branch. Second, amylo-α(1→6)-glucosidase activities which remove glucose molecule at α(1→6) bond. The glucosyl chain is now available again for degradation by glycogen phosphorylase. 12 C. Conversion of glucose-1-phosphate to glucose-6-phosphate This occur by phosphoglucomutase enzyme in the cytosol. In the liver: Glucose-6-phosphate will transported to endoplasmic reticulum, which undergo the action of glucose-6-phosphatase to release the glucose molecule. The glucose produced will transfer from endoplasmic reticulum to cytosol then to blood to help in maintain blood glucose level normal in the blood. 14 In muscle: Glucose-6-phosphate can not be dephosphorylated because of lacking of glucose-6-phosphatase. Instead, it enter glycolysis, providing energy needed for muscle contraction. 15 D. Lysosomal degradation of glycogen A small amount (1-3%) of glycogen continuously degraded by lysosomal enzyme, α(1→4)-glucosidase (acid maltase). Deficiency of this enzyme leads to accumulation of glycogen resulting in a serious glycogen storage disease type II: pomp disease (lysosomal storage disease) 16  Regulation of glycogen synthesis and degradation In the liver, glycogenesis accelerates during periods when the body has been well fed, whereas glycogenolysis accelerates during periods of fasting. In skeletal muscle, glycogenolysis occurs during active exercise, and glycogenesis begins as soon as the muscle is again at rest. 17 18  Hormonal Regulation Glucagon and epinephrine by the last way activate glycogen phosphorylase, and inhibit glycogen synthase under the stimulus of hypoglycemia. Insulin also activate glycogen synthase, and inhibit glycogen phosphorylase, under the stimulus of hyperglycemia. [Note: glucagon has no role in muscle] 19 20 Glycogen Storage Disease Type-I: It is also called Von Gierke’s disease. glycolysis Is due to deficiency of glucose-6-phosphatase. It characterized by: Massive liver enlargement may lead to cirrhosis. Children usually die in early childhood. Treatment is to give small quantity of food at frequent intervals. 21 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 22