1. Glycogen metabolism ط Glycogen synthesis (Glycogenesis) ط Steps involved, Key enzyme ط Glycogen degradation (Glycogenolysis) ط Steps involved, Key enzyme D4 312-30

2. Glycogen Metabolism fig7.51 Glycogen is a branching structure (100,000 glucose) serves as glucose storage of fuel (glucose) in fed state: 400mM glucose (as Glycogen level) is osmotically active cause cell lysis, so cannot store glucose constitutes 1-2% of muscle weight (red & white-rapid), breakdown lead to CO 2 & lactate constitutes 10% of liver weight, breakdown lead to balance blood glucose level Breakdown different from Amylase (uses H 2 O)

4. fig7.52fig7.52 Glu  HK (-ATP)  G6P  PGM-tase  G1P …… Glycogenesis; synthesis of glycogen

5. fig7.56fig7.56 Glygn-tyr 194 + UDP-Glu (PRIMER) : Gly S-ase + Brn Enz ….. Glycogenesis; synthesis of glycogen

6. fig7.55fig7.55 Gly S-ase (α 1,4 glucosidic bond, soluble - AMYLOSE) Branch Enz (α 1,6 glucosidic bond - AMYLOPECTIN)

7. Glycogenolysis; hydrolysis (degradation) of glycogen

8. fig7.53 Gly  Gly P-lase (Pi)  G1P + Gly  De Brn Enz …… Gly P-lase α-1,4 bond (4Glu)  De Brn Enz α-1,6 bond (3+1 Glu) In Muscle yields 1 ATP: Gly + Glu + 1ADP + 1Pi  Gly + 2 Lactate + 1 ATP In Liver yields 0 ATP: Gly + H2O  Gly + Glu + Pi

9. Regulation of Glycogen metabolism ط Regulation of Glycogen synthesis (glycogenesis) ط Regulation of Glycogen degradation (Glycogenolysis) ط Hormonal and Allosteric (non-hormonal) regulation of glycogenesis and glycogenolysis ط Glycogen storage diseases D4 322-30, 317

11. Regulation of glycogen metabolism fig7.58, fig7.57fig7.58fig7.57 1. Allosteric (non-hormonal) - short: § S-ase a (active)  PKs  S-ase b (Pi, inactive): (+) G6P § P-lase b (active)  PKA  Gly P-lase a (Pi, inactive): (+) AMP (–) Glu / ATP

12. Regulation of glycogen metabolism fig7.58, fig7.57fig7.58fig7.57 2. Hormonal - long: S-ase a (active)  PKs  S-ase b (Pi, inactive): (+) cAMP, Ca2+, DAG … (2nd messengers) § S-ase b (Pi, inactive) è P P-tase  S-ase a (active): (+) INS (–) cAMP, Gly P-lase P-lase a (Pi, active)  P P-tase  S-ase b (active): (+) INS (–) cAMP, Gly P-lase § S-ase b (Pi, inactive)  PKA  S-ase a (active): (+) cAMP, Ca2+ (–) INS

13. Summary: (+) S-ase (-) ↑ Glc (+) INS Glg (+) ↓ Glc Anabolism (-) P-lase (+) Catabolism

14. Tissue Receptors 1.Glycogenesis: a) LIVER: fig7.60 Glu-R (P-lase) fig7.67 INS-R b) MUSCLE: fig7.66 INS-R (GLUT4), rapid 2.Glycogenolysis: a) LIVER: fig7.61 GLG-R fig7.61 β-Adg-R (cAMP) fig7.62 α-Andg-R (Ca2+) b) MUSCLE): fig7.64 β-Andg-R (cAMP), rapid & accumulates lactate fig7.65 AC-R (Ca2+)

15. Clinical Correlation: Glycogen Storage Diseases cc7.11 1. Von Gierkes' disease (type I): * Glucoce-6-Phosphorylase deficiency post absorptive hypoglycaemia, lactic academia, hyperlipidemia 2. Pompes' disease (type II): * Lysosomal α 1,4-glucosidase (acid maltase) glycogen granules in lysosomes 3. Cori's disease (type III): * Glycogen de-branching enzyme altered glycogen structure, hypoglycaemia 4. Andersen's disease (type IV): * Glycogen branching enzyme altered glycogen structure 5. McArdle's disease (type V): * muscle Glycogen Phosphorylase muscle glycogen deposition, exercise-induced cramps, fatigue 6. Her's disease (type IV): * liver Glycogen Phosphorylase hypoglycaemia, not severe