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, 6th edition, pages 69-82

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

Complex I Complex III Complex IV

Complex II Complex III

Electron transfer fromComplexes 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 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.