DENTAL%20BIOCHEMISTRY%202015

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DENTAL BIOCHEMISTRY 2015

• OXIDATIVE PHOSPHORYLATION
• Lecture 14
• Michael Lea

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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

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SUGGESTED READING

• Lippincotts Biochemistry, 6th edition, pages
  69-82

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

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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.

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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.

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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.