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 [  (1 —> 4) Linkages]

11. Phosphoglucomutase

12. Glycogen Debranching Enzyme [  (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 B 6 – 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. 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 PP i 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 P i G6P

35. Allosteric Control II

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

37. Glycogen Phosphorylase Bicyclic 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