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Glycogen Metabolism

Glycogen Metabolism. Introduction. Storage Polysaccharides. Why Polysaccharides?. Rapid mobilization Support anaerobic metabolism Animals cannot convert fats to glucose precursors. Why Polymers?. Osmotic Problem!. Glycogen Metabolism. Glycogen Breakdown. Storage Tissues.

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Glycogen Metabolism

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  1. Glycogen Metabolism Introduction

  2. Storage Polysaccharides

  3. Why Polysaccharides? • Rapid mobilization • Support anaerobic metabolism • Animals cannot convert fats to glucose precursors

  4. Why Polymers? Osmotic Problem!

  5. Glycogen Metabolism

  6. Glycogen Breakdown

  7. Storage Tissues • Liver: Glucose for bloodstream • Muscle: Glucose for anaerobic ATP synthesis (Glycolysis)

  8. Pathway Overview • Structure of Glycogen • Glycogen Phosphorylase • Phosphoglucomutase • Glycogen Debranching Enzyme

  9. Structure of Glycogen

  10. Glycogen Phosphorylase[a(1 —> 4) Linkages]

  11. Phosphoglucomutase

  12. Glycogen Debranching Enzyme[a(1 —> 6) Linkages]

  13. Reactions of Glycogen Breakdown

  14. Glycogen Phosphorylase

  15. Reaction of Glycogen Phosphorylase

  16. Mechanism of Glycogen Phosphorylase Binding Crevice Accommodates 4-5 Sugar Residues

  17. Role of Pyridoxal Phosphate(Vitamin B6 – essential cofactor) Function: acid-base catalyst.

  18. Phosphoglucomutase Reaction

  19. Phosphoglucomutase Mechanism

  20. Phosphoglucomutase Regeneration of Glucose-1,6-bisP

  21. Glycogen Debranching Enzyme

  22. Glycogen Synthesis

  23. Phosphoglucomutase

  24. Phosphoglucomutase Mechanism

  25. UDP-Glucose Pyrophosphorylase

  26. Glycogen Synthase I

  27. Glycogen Synthase II

  28. Glycogen Branching

  29. Thermodynamics and Potential Futile Cycle Use hydrolysis of PPi to drive glycogen synthesis!

  30. Control of Glycogen Metabolism Glycogen Synthase Glycogen Phosphorylase Why not UDP-Glucose Pyrophosphorylase?

  31. Regulatory Mechanisms Allosteric Control Covalent Modification

  32. Covalent Modification I(Phosphorylase)

  33. Covalent Modification II(Glycogen Synthase)

  34. Allosteric Control I EnzymeNegativePositive Phosphorylase a (more active) Glucose Phosphorylase b (less active) ATP G6P AMP Gycogen Synthase a (high activity) Glycogen Synthase b (low activity) ADP Pi G6P

  35. Allosteric Control II

  36. Advantages of Covalent Modification • Sensitivity to more allosteric effectors • More flexibility in control patterns • Signal amplification

  37. Glycogen PhosphorylaseBicyclic Cascade

  38. Formation of Cyclic AMP (cAMP)

  39. Activation of Phosphorylase Kinase

  40. Activation of Phosphorylase Signal Amplification

  41. Inactivation of Phosphoprotein Phosphatase I Importance of Protein-Protein Interactions

  42. Glycogen Synthase Bicyclic Cascade

  43. Control of Glycogen Synthase

  44. Integration of Glycogen Metabolism Control Mechanisms • Blood Glucose Levels (Liver) • Insulin • Glucagon • Tissue Glucose Levels (Stress) • Epinephrine • Norepinephrine

  45. Maintenance of Blood Glucose Levels • Insulin (peptide from the pancreas) • Produced in response to high glucose • Insulin-dependent glucose transporter (GLUT4) • cAMP decreases • Glucagon (peptide from the pancreas) • Produced in response to low glucose • Glucagon receptors (liver) - activation of adenylate cyclase • Glycogen breakdown to glucose-6-P • Glucose-6-phosphatase • Glucose enters bloodstream

  46. Response to Stress(Muscle and Other Tissues) • ß-adrenergic receptors (muscle and other tissue) • Activation of Adenylate Cyclase • Glucose-6-P for glycolysis • Stimulates pancreatic cells to produce glucagon

  47. Stress Hormones(Adrenyl Gland)

  48. Glycogen Storage Diseases

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