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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
TRANSPORT OF ELECTRONS FROM NADH
TO OXYGEN
ΔG° = - n F ΔE°
Where
n= numbe r of electro ns transferred
F = Farada y constan (2t 3,062 calori /es volt/mole)ΔE° = standar d redo x potentia l of theelectron
acceptor – thestandar d redo x potentia l of the
electr ondonatin g pair
NAD+/NADH E° = -0.32 v1/2 O2/ H2O E° = +0.82 v
ΔG° = - 2 x 23,0 62 1x .14
= - 52,581 caloriesSinc e theΔG° fo r hydrolysi s of ATP is about
730 0 calories, itm ay b e anticip ated tha t theoxidati on o f NA DH ca n becoupl ed to the
synthesi s ofsevera l molecule s of AT .P
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 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.