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Glycogen Metabolism Storage and Mobilization of Glucose

Glycogen Metabolism Storage and Mobilization of Glucose. NUTR 543 – Advanced Nutritional Biochemistry David L. Gee, PhD Professor of Food Science and Nutrition Department of Health, Human Performance, and Nutrition Central Washington University. Glycogen Functions. Liver

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Glycogen Metabolism Storage and Mobilization of Glucose

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  1. Glycogen Metabolism Storage and Mobilization of Glucose NUTR 543 – Advanced Nutritional Biochemistry David L. Gee, PhD Professor of Food Science and Nutrition Department of Health, Human Performance, and Nutrition Central Washington University

  2. Glycogen Functions • Liver • Buffer for regulating blood glucose levels • Muscle • Store of glucose as a fuel for exercise • high intensity exercise dependent on anaerobic glycolysis

  3. Glycogen SynthesisFigure 12-2

  4. Regulation of Glycogen SynthaseFigure 12-4 • Active/Inactive Forms • Active • dephosphorylated • Inactive • phosphorylated

  5. Regulation of Glycogen SynthaseFastingFigure 12-4 • Glucagon or epinephrine • G-protein linked receptors • increased [cAMP]

  6. Regulation of Glycogen SynthaseFastingFigure 12-4 • cAMP activates Protein Kinase A • Protein kinase A phosphorylates and inactivates glycogen synthase • Little glycogen synthesis during fasting

  7. Regulation of Glycogen SynthaseFeedingFigure 12-4 • Insulin • Reduces [cAMP] • Stimulates phosphodiesterase • Induces and activates protein phosphatase-1 • Activates GS • Feeding results in glycogen synthesis

  8. Glycogen Degradation • Glycogen Phosphorylase • Hydrolyzes glucose units from glycogen • Produces glucose-1-P • Removal of branch points • Debranching enzyme complex • Glucan transferase • Alpha-1,6-glucosidase

  9. Regulation of Glycogen PhosphorylaseFastingFigure 12-7 • Glucagon or epinephrine • Increase [cAMP] • Activates Protein Kinase A • Phosphorylates and activates glycogen phosphorylase • Fasting results in increased glycogenolysis

  10. Regulation of Glycogen PhosphorylaseFeedingFigure 12-7 • Insulin • Reduces [cAMP] • Induces and activates Protein Phosphatase-1 • Inactivates Glycogen Phosphorylase • Feeding results in decreased glycogenolysis

  11. Allosteric Regulation of Glycogen PhosphorylaseTable 12-1

  12. Regulation of Glycogen Degradation during ExerciseFigure 12-8

  13. Coordinated Regulation of Glycogen Metabolism (Table 12-2)

  14. Application:Pharmacological Agents for Diabetics • Insulin • Mandatory for Type 1 diabetics • Used in Type 2 diabetics as oral medications become less effective • Oral medications • Mechanisms • Increase insulin production • Improve insulin receptor sensitivity • Inhibit gluconeogenesis • Inhibit carbohydrate absorption

  15. Sulfonylureas • First widely used diabetic drug • Stimulates endogenous release of insulin from pancreas • Direct action on ATP-K channel protein on beta-cells • Short and longer acting forms • Glipizide (Glucotrol), glyburide (Diabeta), tolazamide (Tolinase) • Side Effects • Hypoglycemia • Weight gain

  16. Meglitinides • Like sulfonylureas, stimulate pancreatic secretion of insulin • Short-acting: taken with meals • Replaglinide (Prandin) • Side Effects • Hypoglycemia • Weight gain

  17. Biguanides • Mechanism of action • Reduces gluconeogenesis (stimulates (?) Protein kinase A) • Decrease absorption of dietary CHO • Increase insulin sensitivity • Metformin (Glucophage) (most widely used anti-diabetic drug) • Side effects (not hypoglycemia) • Lactic acidosis • Contraindicated in heart failure, liver and kidney disorders • Diarrhea • Other facts • Only drug shown to reduced risk diabetes related heart disease • Derived from French lilac (known as useful for treating symptoms of diabetes)

  18. Thiazolidinediones (TZDs) • Mechanism of action • Binds to nuclear receptors that increase transcription of certain genes • Decreased insulin resistance • Leptin levels decreased (increased appetite) • Rosiglitazone (Avandia) • Side effects: edema, risk of hepatitis, increased heart disease risk (5/07 – FDA safety alert)

  19. Incretin mimetic • Incretins are GI hormones that increase insulin production • Exenatide (39aa peptide from saliva of gila monster (lizard spit), synthesized) • 50% homology with Glugacon-Like Peptide (GLP), an incretin that stimulates insulin production and inhibits glucagon production • Self-regulating: active only when during hyperglycemia • Appetite suppresent effect: gradual weight loss • Side effects: • may increase hypoglycemic risk with sulfonylureas • must be injected 2x per day

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