Respiratory chain and oxidative phosphorylation + Glycogenesis and Glycogenolysis

1. Respiratory chain and oxidative phosphorylation + Glycogenesis and Glycogenolysis

2. Respiratory chain (RCH) • is located in a mitochondrion • needs oxygen (O2) for its function

3. the mitochondrion contained the enzymes responsible for electron transport and oxidative phosphorylation mitochondrion In inner membrane knobs Impermeable to ions and most other compounds

4. Electron Transport (Respiratory) Chain • Electron transport chain (ETC) or respiratory chain (RC) functions to oxidize NADH and FADH that arise from different metabolic pathways carried out on nutrients, leading to release of energy(exergonic). • Part of the released E is used for the synthesis of ATP (oxidative phosphorylation).

5. Components Of The Electron Transport Chain: • can transfer either H or electrons • are called Complex I, II, III and IV --------------------------------------------------------------------------------------------- The Four Electron Transport Complexes in the Inner Mitochondrial Membrane Respiratory Chain ---------------------------------------------------------------------------------------------- (a) Complex I NADH-CoQreductase (ATP) (b) Complex II SuccinateCoQreductase (no ATP) (c) Complex III CoQ- Cytochrome C reductase, (ATP) (d) Complex IV Cytochrome C oxidase (ATP)

6. Two small electron carriersare also needed to link these large complexes, they are: 1.Coenzyme Q (CoQ or ubiquinone) • the only electron carrier not bound to a protein. 2.Cytochrome c • Cytochromesare electron carriers containing hemes . • Cytochrome c is a small, water-soluble protein.

7. proton= H+ electron= e- The figure is adopted from the book: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

8. Operation of the Electron Transport (Respiratory) Chain The transfer of electrons is not directly to oxygen but through coenzymes. • Complex I transfers H+ into an intermembrane space • Coenzyme Q accepts e- from both Complex I and Complex II • Complex IV transfers electrones to oxygen • oxygen is reduced to H2O

9. proton= H+ electron= e- The figure is adopted from the book: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

11. The function of the RCH • is to regenerate NAD+ from NADH • is to regenerate FAD from FADH2 • oxygen is reduced to H2O • is to finish oxidation of energy substrates and conserve their energy in a form of ATP

12. Oxidative Phosphorylation • Coupling of the electron transport in RCH with phosphorylation of ADP to form ATP. • needs proton gradient on the inner mitochondrial membrane by RCH • is catalyzed by ATP synthase

14. Mechanism of Oxidative Phosphorylation 1- During the ETC (located at the inner mitochondrial membrane) , H+ are released into the intermembrane space (outside inner mitochondrial membrane). 2- The inner mitochondrial membrane is impermeable to H+, which accumulate outside the membrane.

15. 3- An electrochemical gradient is creating across the membrane. An electrical gradient (with more positive charges on the outside of the membrane than on the inside ) and chemical gradient or pH gradient (the outside of the membrane is at lower pH than the inside). 4- This H+ gradient is used by the ATP synthase complex to make ATP via oxidative phosphorylation.

18. On the the Inner Mitochondrial Membrane, theATP Synthase Uses the Proton Gradient Generated by Electron Transport of the Respiratory Chain to Synthesize ATP Electron transport chain

19. ATP yield from oxidative phosphorylation accounts for approximately 85% of the maximal 38 ATP generated in complete oxidation of glucose to CO2. • 1 NADH 3ATP • 1 FADH 2ATP

20. Glycogen metabolism Glycogenesis and Glycogenolysis

21. Glycogen • Glycogen is the main storage form of carbohydrates in animals. It is present mainly in liver and muscle. • The total quantity of muscle glycogen is more than liver glycogen, because of the large muscle mass. • The glycogen is present in the cytoplasm of the cell, because all the enzymes related to glycogen metabolism are cytoplasmic.

22. Function of glycogen: • The function of liver glycogenis to maintain the blood glucose concentration (acts as a glucose buffer). • The function of muscle glycogenis to serve as a fuel reserve for synthesis of ATP during muscle contraction (as energy store).

23. Glycogen is a polymer of glucose residues linked by • α-1:4 glycosidic bonds, mainly • α-1:6 glycosidic bonds, at branch points. - Glycogen branches contain about 8 -12 glucose residues.

24. Glycogen synthesis (glycogenesis) • Glycogen is synthesized from D-glucose in muscle and liver. • Its site in the cytoplasm of every cells mainly liver and muscle

25. Steps of Glycogen synthesis (glycogenesis): 1-Activation of glucose: • UDP-glucose(the active form of glucose) is formed from glucose 1-phosphate and UTP (Uridine triphosphate) by UDP-glucose pyrophosphorylase. UDP-glucose is the source of all glucosyl residues that are added to the growing glycogen molecule.

27. 3- Glycogen synthase: Activated glucose units, UDP-glucose, are sequentially added by glycogen synthase to glycogen primermolecule(short linear glucose polymer). The glycogen synthase can add glucose units in only 1,4-linkages. Glycogen primer (n) + UDP-glucose ---- Glycogen (n+1) + UDP.

28. Glycogen synthesis 4- Branching enzyme: When the chain has been lengthened, the branching enzyme transfers a part of the α1:4 chain to a neighbouring chain to form an α l :6 glucosidic link. Thus establishing the branching points in the molecule. The branches grow by further addition of 1:4 glucosyl units.

29. Degradation of glycogen (glycogenolysis) • It is the breakdown of glycogen into glucose in liver and lactic acid in muscles. 1- Glycogen Phosphorylasecatalyzes phosphorolyticcleavage of the α(14) glycosidic linkages of glycogen, releasing glucose-1-phosphate as reaction product. Glycogen(n) + Pi Glycogen (n–1) + glucose-1-phosphate

30. Glycogenolysis 2)- Debranchingenzyme is hydrolytic enzyme acts on α1 - 6 glycosidic link giving free glucose. 3)- G-1-P is converted into G-6-P by the action of phosphoglucomutase. • In liver, G-6-P is hydrolysed by the action of G-6-phosphatase free glucose (diffuse from liver cell to blood stream) • In muscle, G-6-P by glycolysis lactic acid because absence of G-6-phosphatase

31. The rate limiting enzymes controlling glycogen metabolism are: • 1. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis. • 2. Glycogen synthase catalyzes the rate-limiting step in glycogenesis.

32. Glycogenolysis • Muscle glycogen functions to provide muscle with glucose during contraction. . • Liver glycogen functions to maintain blood glucose between meals. • After 12 -18 hr fasting, liver glycogen whereas muscle glycogen is after prolonged exercise.

33. Difference between muscle and liver glycogen