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DENTAL BIOCHEMISTRY 2015

DENTAL BIOCHEMISTRY 2015. OXIDATIVE PHOSPHORYLATION Lecture 14 Michael Lea. LECTURE OUTLINE. Reduced NAD and FAD are oxidized via the mitochondrial electron transport chain A proton gradient is established across the inner mitochondrial membrane The proton gradient drives ATP synthesis

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DENTAL BIOCHEMISTRY 2015

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  1. DENTAL BIOCHEMISTRY 2015 OXIDATIVE PHOSPHORYLATION Lecture 14 Michael Lea

  2. LECTURE OUTLINE • Reduced NAD and FAD are oxidized via the mitochondrial electron transport chain • A proton gradient is established across the inner mitochondrial membrane • The proton gradient drives ATP synthesis • Inhibitors of electron transport block ATP synthesis • There are compounds that can uncouple electron transport from ATP synthesis

  3. SUGGESTED READING • Lippincott’s Biochemistry, 6th edition, pages 69-82

  4. Complex I Complex III Complex IV Electron transfer from Complexes I and II Complex II Complex III

  5. INHIBITORS OF OXIDATIVE PHOSPHORYLATION • Complex I : Rotenone • Complex III: Antimycin A • Complex IV: Carbon monoxide and Cyanide • Complex V (ATP synthase): Oligomycin • ATP: ADP Translocase (Antiporter): Atractyloside

  6. UNCOUPLERS OF OXIDATIVE PHOSPHORYLATION • Agents that dissipate the proton gradient across the inner mitochondrial membrane prevent ATP synthesis but permit electron transport. • Energy is released as heat. • Examples are 2,4-dinitrophenol and Uncoupling Protein I (thermogenin), a compound in the mitochondria of brown adipose tissue.

  7. DISEASES ASSOCIATED WITH DEFECTS IN CELL RESPIRATION AND OXIDATIVE PHOSPHORYLATION • Hereditary defects in cell respiration and oxidative phosphorylation are very rare. They tend to result in lactic acidosis and muscle and nerve pathology. • Examples are Lebers hereditary optic neuropathy and Leigh syndrome.

  8. LECTURE OBJECTIVES • After studying this lecture material you should be able to • Describe how reduced NAD and FAD are oxidized via the mitochondrial electron transport chain • Identify the different and common aspects of electron transfer to oxygen from NADH and FADH2 • Describe how a proton gradient is established across the inner mitochondrial membrane and understand that this gradient drives ATP synthesis • Describe the action of inhibitors and uncouplers of mitochondrial electron transport and distinguish the effects of these two types of agents on electron flow • Describe the consequences of hereditary defects in oxidative phosphorylation.

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