2. Introduction to Metabolism 1 By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

3. General Objectives  Metabolic pathways for carbohydrates  Hormonal control & enzyme regulation  Introduction to Metabolism  Mitochondria: ATP production & ETC

4. Specific Objectives  Biochemical reaction and Δ G  E-Coupled reactions using ATP  Mitochondria: Structure  Electron Transport Chain (ETC)  Oxidative phosphorylation  Mitochondria: Clinical correlations

5. Free Energy Change Δ G Exergonic Spontaneous E-Loss Endergonic Not spontaneous E-Gain

6. Coupled Reactions

7. Adenosine Triphosphate (ATP) Δ Gº -7.3 kcal/mol/bond

8. Oxidative Phosphorylation for ATP Production E-rich compounds e.g., Oxidation E-rich reduced coenzymes ETC

9. Mitochondria

10. Electron Transport Chain Non-protein mobile carrier Electron transport and ATP synthesis are tightly coupled processes

11. Electron Transfer Hydride ions (:H - ) to NAD + Hydrogen atom (.H) to FMN, Co-Q and FAD Electrons (.E - ) to cytochromes

12. NAD + / NADH

13. Oxidation/Reduction Oxidation: Loss of hydrogen Loss of electrons Reduction: Gain of hydrogen Gain of electrons

14. Redox Pair

15. Redox Pair and Electron Flow Electron transfer down ETC is energetically favored

16. P:O Ratio  ATP made / O atom reduced  P:O for NADH 3:1  P:O for FADH 2 2:1  The remaining of E during electron transport used for Ca transport released as heat

17. Chemiosmotic Hypothesis

18. Electron transport coupled to ADP phosphorylation (ATP synthesis) Common intermediate: Proton pump Proton pump: Electrical & pH gradients Proton re-entry: Via F ° channel Conformational changes & ATP synthesis Dissipating electrical & pH gradients

19. Uncoupling Proteins (UCPs)

20. UCP1 : Thermogenin Abundant in brown adipose tissue Cold or birth leads to Fatty acid oxidation and heat production

21. Mitochondria: Clinical Correlations Inherited defects in oxidative phosphorylation: 13 mtpolypeptides encoded by mtDNA 107 mtpolypeptides encoded by nuclear DNA mtDNA: maternally inherited 10x prone to mutations Mitochondrial myopathies Mitochondria and apoptosis: Cytochrome c (cytosol) & proapoptotic caspases