GLYCOGEN

1. GLYCOGEN

2. Glycogen Glycogen Metabolism Liver and Muscle What Glucose Glycogenesis  G-6P Glycolysis Glycogenolysis Pyruvate Bridging Rx. AcetylCoA NAD+/FAD NADH/FADH2 C6 C4 OP Krebs Cycle ADP O2 C5 C4 ATP

3. Glycogen Storage Liver (10%) ← where → Muscle (2%) maintains glucose reserve to meet own anaerobic energy needs. maintains glucose reserve for blood ← why → Glycogen Storage – When (Glycogenolysis) fasting state glucagon stimulates phosphorylase glucagon suppresses glycogen synthase exercise state epinephrine stimulates phosphorylase Exercise induces ↑Ca2+ which ↑phosphorylase Glycogen Storage – When (Glycogenesis) fed state Excess glucose → glycogen Fed state Insulin ↑glucose (GLUT) and ↑glycogenesis

4. Glycolysis& Glycogen Glucose Glucose-6-P DHAP Pyruvate Glycogen

5. Glycogenesis Phosphoglucomutase Glucose-1-P + UTP PPi 2Pi UDP-Glucose + Glycogenn(Glycogen Synthase) Glycogen(n+1) Glycogenolysis Glucose-6-P Glycogen(n+1) Phosphorylase transferase a 1-6 glucosidase Glycogenn + Glucose-1-P + (Glucose) Phosphoglucomutase Glucose-6-P Glucose-6-Phosphatase Liver only Glycolysis Muscle Glucose + Pi Pyruvate

6. P P P P P P Phosphorylase

7. No Phosphate Transferase a-1,6 glucosidase

8. P P P P P P Glucose-6-P P P P P P P Glucose-1-P Phosphoglucomutase

9. export Muscle (glycolysis enzymes) Glycolysis& Glycogen Glucose Glucose-6-P DHAP Pyruvate Liver– glucose-6-phosphatase Glycogen glucose-6-phosphatase is used both for liver glycogenolysis and gluconeogenesis

10. To Blood Glucose Transporter Liver Cell Membrane Glucose-6 Phosphatase P Fasting State = lower [glucose] in blood Fasting State = higher [glucose] in liver cells

11. Glucose-6-phosphate is dephosphorylated in the liver for transport out of the liver

12. Global Metabolic Regulation Allosteric―internal signals affect enzyme rates Hormones ―External signals that bind to specific cell receptors to alter cell metabolism. Insulin GlucagonEpinephrine Muscle: ↑Glut↑Glycogenolysis Liver ↑Glycogenesis↑Glycogenolysis ↑Glycolysis↓Glycolysis ↓Gluconeogenesis↑Gluconeogenesis Adipose ↓Triglyceride breakdown ↑Triglyceride breakdown ↑Triglyceride breakdown ↑fatty acid synthesis ↓fatty acid synthesis↓fatty acid synthesis

13. INSULIN Made in Pancreas (Islet Cells) ― ↑[Glucose] signals release (Fed State) # muscle glucose transporter ― Outcome : less blood glucose

14. INSULIN signal transduction cascade

15. Global Metabolic Regulation Allosteric―internal signals affect enzyme rates Hormones ―External signals that bind to specific cell receptors to alter cell metabolism. Insulin GlucagonEpinephrine Muscle: ↑Glut↑Glycogenolysis Liver ↑Glycogenesis↑Glycogenolysis ↑Glycolysis↓Glycolysis ↓Gluconeogenesis↑Gluconeogenesis Adipose ↓Triglyceride breakdown ↑Triglyceride breakdown ↑Triglyceride breakdown ↑fatty acid synthesis ↓fatty acid synthesis↓fatty acid synthesis

16. GLUCAGON Epinephrine Adrenal gland: Tyr derivative Secreted by  emotional state Binds Muscle Receptor + Activates Glycogenolysis Anticipation of anaerobic activity Also stimulates glucagon release Prancreatic Peptide 29aa Secreted when low [glucose] Binds Liver Receptor Activates Phosphorylase Deactivates Glycogen Synthetase

17. R &/or Ca++ PK PK ATP cAMP adenylatecyclase g b a G-Syn G-Syn Phos Phos P P Epinephrine Cascade cAMP= allosteric PK = covalent mod. Epinephrine (E) E

18. The Glucagon/Epinephrine Signal Transduction Cascade Hormone binds to its receptor at cell surface G-Protein activated (a-GTP released) a-GTP activates adenylate cyclase: ATP  cAMP cAMP is allosteric regulator of Protein Kinase 1 Protein Kinase 1 activates (by phosphorylation) phosphorlyaseKinase (abgd)  a(b-P)gd muscle activity Ca2+abgdabg(d-Ca2+) Phosphorylasekinase activates Phosphorylase and deactivates Glycogen Synthase.

19. Phos Phos Phos P P G-Syn G-Syn P How are Glucagon effects reversed (liver)? Glucose (G) Protein Phosphatase I or PhosphorylasePhosphatase G

20. How is muscle Glycogenolysis reversed? Insulin (cascade) activates Protein Phosphatase 1 (as opposed to gluconeogenesisas in liver) Phosphorylase deactivated Glycogen Synthaseactivated

21. Insulin – glucose into muscle/adipose Glucagon – liver exports glucose adipose exports fatty acids [Glu] blood Meal Glycogen broken down to provide glucose Fed 60 – 100 mg/dL ~2 hrs ~12 hrs

22. high glycemic index diabetic [Glu] blood Meal Fed 60 – 100 mg/dL ~2 hrs ~12 hrs

23. early long term ~ 3 days late Lipolysis Brain uses Ketone bodies Protein conserved Fasting State Glycogen broken down to provide glucose glycogenolysis Protein broken down to make glucose gluconeogenesis

24. Metabolic Disorders Congenital a) gene is inactivated – protein is absent b) gene is under expressed (TF?) – less protein made c) gene is mutated – protein capability decreased Acquired a) autoimmune disorders (e.g. Type I diabetes) b) triggered apoptosis (e.g. oxidative stress) Which pathway is more important to your long term health? a) Glycogenolysis in the liver b) Glycogenolysis in muscle c) Gluconeogenesis in the liver

25. Which pathway is more important to your long term health? a) Glycogenolysis in the liver b) Glycogenolysis in muscle c) Gluconeogenesis in the liver Which disease is more detrimental to your health? a) McArdle’s (V) b) Hers’ (VI) c) Von Gierke’s (I)

26. Suggest a possible solutions for McArdle’s disease Why is growth poor in Hers disease? Suggest possible solutions for Hers’/Von Gierke’s disease