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Biochemistry Dr. Aws Hassan 3rd Lecture Glycogen Metabolism Glycogen molecule : ● Glycogen is the major storage form of carbohydrate in animals . ● Glycogen is stored as globular granules in the cytoplasm of the cells ; mainly in the liver (10gm/100gm tissue ) and in the muscle (1-2gm/100gm tissue ) . The total quantity of muscle glycogen is more than liver glycogen because of the large muscle mass . ● Glycogen molecules are highly branched polymers consisting of D-glucose residues . The linkage between glucose residues is α-1,4 except at branch points where the linkage is α-1,6 . ● Each branch chain contains about 12 glucose residues . ● Branching occur at intervals of about every 4 – 6 molecules . ● Branching is so organized that it makes glycogen less space occupying . ● Because of this high branching , the glycogen molecule is capable to store and deliver glucose units quickly . Glycogen synthesis (Glycogenesis) : ● The precursor for glycogen synthesis is activated glucose ( UDP – glucose ) : glucokinase isomerase Glucose ------------------→ Glucose–6–p -----------------→ Glucose–1–p Glucose–1–p + UTP ---------------------→ UDP – glucose + PPi Pyrophosphate Glycogen degradation ( Glycogenolysis ) : The enzymes involved in glycogen degradation are : 1- Glycogen Phosphorylase ( Rate – Limiting enzyme ) : This enzyme uses inorganic phosphate (Pi ) to phosphorylate and cleave α-1,4 bonds and glucose residues are released as glucose-1-p . 2- Debranching enzyme : This enzyme has two activities : a - 4:4 transferase activity : Cleaves α-1,4 bond and forms a new α-1,4 bond : removes three of the four glucose residues remained away from one branch point and transfers it to the end of the other branch chain . b - α-1,6 glucosidase activity : Hydrolyze the last glucose residue at the branch point ( linked by α-1,6 bond ) and free glucose released . Notes : ● Degradation of glycogen in both liver and muscle leads to 90% of glucose residues being released as glucose-1-p and 10% as free glucose . ● In Liver ; Glucose-1-p produced from glycogen degradation is isomerized to glucose-6-p .Then , inorganic phosphate is cleaved from glucose-6-p by the enzyme glucose-6-phosphatase ( present in liver & kidney ) and free glucose is released and enters the blood . Therefore , liver glycogen is utilized to maintain blood glucose during fasting . ● Muscles do not contain the enzyme glucose-6-phosphatase and therefore cannot contribute directly to the maintenance of blood glucose . In muscles , glycogen is degraded to provide ATP for the activity of muscle itself (muscle contraction) . Time scale for gluconeogenesis & glycogenolysis : ■ The liver begins to breakdown its glycogen stores by the process of glycogenolysis after 2-3 hours after a meal . ■ Glycogenolysis is the major process responsible for maintaining blood glucose until 18-20 hours fast . ■ The liver begins the process of gluconeogenesis after about 4-6 hours of fasting . ■ Glycogenolysis & Gluconeogenesis contribute equally for maintaining blood glucose at the period between 18-20 hours of fast . ■ Gluconeogenesis become the major process for maintaining blood glucose after 18-20 hours of fasting . ■ After about 30 hours fast liver glycogen is completely depleted and gluconeogenesis become the only source of blood glucose . ■ Muscle glycogen is depleted after about 15 minutes of heavy exercise . Glycogen Storage Diseases ( Glycogenosis ) A group of inherited disorders characterized by deposition of an abnormal type or quantity of glycogen in tissues . Type I – Von Gierk’s disease : ● The enzyme glucose-6-phosphatase is deficient . Incidence is 1 in 100,000 birth . ● Both liver and renal tubules are loaded with glycogen . Liver enlargement may lead to cirrhosis . ● Glucose-6-phosphate is accumulated but glucose cannot be released from liver during overnight fast leading to fasting hypoglycemia . ● Because glucose becomes less available to cells , therefore , the energy is obtained from fat metabolism and increasing amount of acetyl-CoA is formed which is mostly utilized in the synthesis of ketone bodies ( ketosis ) . [ Glycogen synthesis ( glycogenesis ) & Glycogen degradation ( glycogenolysis ) ]