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 Inhibitors of electron transport block ATP synthesis There are compounds that can uncouple electron transport from ATP synthesis

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

Complex I Complex III Complex IV Complex IIComplex III Electron transfer from Complexes I and II

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

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.

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.

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 FADH 2 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.