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Glycogen Metabolism

Glycogen Metabolism. Objectives:. Why do we need to store carbohydrates? Why carbohydrates are stored as glycogen? Overview of glycogen synthesis (Glycogenesis) Overview of glycogen breakdown (Glycogenolysis) Key elements in regulation of both Glycogenesis and Glycogenolysis.

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Glycogen Metabolism

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  1. Glycogen Metabolism

  2. Objectives: • Why do we need to store carbohydrates? • Why carbohydrates are stored as glycogen? • Overview of glycogen synthesis (Glycogenesis) • Overview of glycogen breakdown (Glycogenolysis) • Key elements in regulation of both Glycogenesis • and Glycogenolysis

  3. What do we really need? • A constant source of glucose is mandatory for : • Brain • Cells with few or no mitochondria • Exercising muscles (anaerobic glycolysis)

  4. GLycogen

  5. GlycogenA storage form of glucose

  6. Glycogen is stored in granules in the cytosol of primarily the liver and skeletal muscles.

  7. In liver : 10% of the fresh weight in the well-fed adult liver (100g) After 12-18 hrs of fasting ,almost depleted In skeletal muscle : 1-2 % of fresh weight of resting muscle ( 400 g) Depleted after prolonged vigorous exercise Moderately decreased by prolonged fasting (weeks) Stores of Glycogen

  8. Thus Liver glycogen : is used to buffer the overall blood glucose level; glycogen is degraded (with the resulting glucose released into the blood stream) during the early stages of a fast. Muscle : uses its glycogen stores for (ATP) energy during strenuous exercise.

  9. Structure of Glycogen

  10. – It is a highly branched –chain homopolysaccharide made from α-D glucose .

  11. Amylose is the linear unbranched molecule of glucosyl residues attached byα(1→4) linkages. • Glycogen hasbrancheslocated on average eightglucosyl residues resulting in highly branched moleculewhich leads to : • More soluble • Increase rate of degradation • Increase rate of synthesis

  12. Metabolism of Glycogen in Skeletal Muscle Glycogenesis: Synthesis of Glycogen from Glucose Glycogenolysis: Breakdown of Glycogen to Glucose-6-phosphate

  13. Glycogen Synthesis (Glycogenesis)

  14. Site : cytosol • It requires ATP &UTP • 1- Building blocks: UDP-GLUCOSE • 2- Initiation of synthesis • Elongation of pre-existing glycogen fragment • OR • The use of a protein glycogen primer (glycogenin) • (Glycogen synthase cannot initiate synthesis but only elongates pre-existing glycogen fragment or glycogen primer (glycogenin) • 3- ELONGATION: Glycogen synthase (for a1-4 linkages) • 4- BRANCHING: Branching enzyme (for a1-6 linkages

  15. Glycogen BreakdownGlycogenolysis

  16. 1- Shortening of glycogen chain: phosphorylase Cleaving of a(1-4) bonds of the glycogen chain producing glucose 1-phosphate Glucose 1-phosphate is converted to glucose 6-phosphate (by mutase enzyme) Pyridoxal phosphate (vit -B6

  17. 2- Removal of branches : bydebranching enzymes • Cleaving of a(1-6) bonds of the glycogen chain producing free glucose (few) • 3- Fate of glucose 6-phosphate (G-6-P): • - G-6-P is not converted to free glucose • - It is used as a source of energy for skeletal muscles during muscular exercise (by anaerobic glycolysis starting from G-6-P step) • ( in case of liver glucose-6-phosphatase converts G6P to glucose

  18. Regulation

  19. Regulation of Glycogen Metabolism Synthesis & degradation of glycogen are tightly regulated In Skeletal Muscles: • Glycogen degradation occurs during active exercise • Glycogen synthesis begins when the muscle is at rest • Regulation occurs by 2 mechanisms: 1- Allosteric regulation 2- Hormonal regulation (Covalent modification)

  20. Regulation ofGlycogen Metabolism 1. Allosteric Regulation

  21. Regulation ofGlycogen Metabolism Increase of calcium during muscle contraction Formation of Ca2+ -calmodulin complex Activation of Ca2+ -dependent enzymes, e.g., glycogen phosphorylase

  22. Regulation of Glycogen Metabolism: 2. Hormonal Regulation by Epinephrine Muscle contraction Epinephrine release Skeletal muscle: Epinephrine/receptor binding Second messenger: cAMP Response: Enzyme phosphorylation P P Glycogen synthase (Inactive form) Inhibition of glycogenesis Glycogen phosphorylase (Active form) Stimulation of glycogenolysis

  23. Glycogen Storage DiseasesGSD Type V (Mc Ardle Syndrome) • Deficiency of skeletal muscle glycogen phosphorylase

  24. Thank You

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