SURVEY OF BIOCHEMISTRY Electron Transport and Oxidative Phosphorylation

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SURVEY OF BIOCHEMISTRYElectron Transport and

Oxidative Phosphorylation

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Redox Centers

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The Mitochondrion

Zoom in on the cristae:

~2000 per cell

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How does electron transfer work?

NADH binds to Complex I on the matrix side

of the membrane

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Electron Transfer with NADH

NADH transfers its e-

to redox centers in Complex I

2e- go to FMN…

FMN resembles FAD without the adenine dinucleotide group

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Electron Transfer with FMNH2

NADH transfers 2e-

to FMN - a redox center in Complex I

FMNH2 can then pass each e- to series of Fe-S clusters in a stepwise manner:

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Fe-S Clusters in Complex I

Complex I contains Fe-S clusters as cofactors

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Coenzyme Q (Ubiquinone)

Electrons pass from Fe-Sclusters to a “mobile”

electron carrier cofactor called Coenzyme Q

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Electron Transfer with CoQ

Coenzyme Q initially binds to Complex I to pick up 2 e- from the Fe-S clusters in Complex I

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Complex II

Succinate-Coenzyme Q Oxidoreductase

FADH2

Complex II is notshown

Electrons pass fromFADH2 to CoQvia Complex II

4H+ ions get pumped out of the matrix by

Complex I and CoQbut not Complex II

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Electron Transfer with CoQ

Coenzyme Q binds to Complex III on the

Intermembrane space side

One e- goes to Cytochrome c

One e- goes into the Q

cycle

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Electron Transfer with Cyt c

Once CoQ loses its 2e-,

it can dissociate from the

upper region of Complex

III and rebind near the

matrix sideand pick up the e- it just

donated!

Meanwhile, Cytochrome c carries its

e- to Complex IV

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Electron Transfer with Cyt c

Another CoQ carrying 2e- can bind to Complex III, passing one of its e- to Cytochrome c and one into the Q cycle and ultimately to the

original CoQ molecule.

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Proton Pumping from Matrix

NADH FMN Fe-S CoQ

4 H+ ions get pumped from matrixinto the intermembrane space

as 2 electrons are passed through Complex I

(mechanism unknown)

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Complex III and Complex IV

Cytochrome bc1

O2 + 4 H+ 2H2O

Cytochrome c oxidase

How does ATP get made?

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Chemiosmotic Theory

Idea that the free energy needed to transport e- is conserved by the formation of a transmembrane

proton gradient.

Proton gradient drives ATP synthesis.

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Complex V: ATP Synthase

F1F0 ATPase

F0 - water insolublew/ 8 types of subunits

F1 - water solubleperipheral membraneprotein w/ 5 types of

subunits

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Binding Mechanism in ATP Synthase

O = open L = loose T = tight

1. ATP binds into the T protomer first2. ADP and Pi bind to the L protomer3. Supply of energy induces a conformational change4. ATP goes to the O protomer and is released5. ATP is synthesized at the T protomer

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Overview of Electron Transport

Notice theseinhibitors of

electron transport!

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Coordinated Control of Glycolysis and the TCA Cycle

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Pros and Cons of Aerobic Metabolism

Anaerobic Metabolism of Glucose:

C6H12O6 + 2 ADP + 2 Pi 2 Lactate + 2 H+ + 2 H2O + 2 ATP

Aerobic Metabolism of Glucose:

C6H12O6 + 32 ADP + 32 Pi + 6O2 6 CO2 + 38H2O + 32 ATP

PRO: Aerobic metabolism is up to 16x more productivethan anerobic metabolism!

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Pros and Cons of Aerobic Metabolism

O2 + e- O2-•

CON: Aerobic metabolism, with its high efficiency, tendsto produce free radicals of oxygen!

Superoxideradical

Other harmful possibilities:

H2O2 + Fe2+ •OH + OH- + Fe3+

O2-• + H2O2 O2 + H2O + •OH

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Superoxide Dismutase (SOD)

• An inherent antioxidant enzyme

2O2-• + 2H+ O2 + H2O2

Catalase

SOD

2H2O2

2 H2O + O2

Otherpotential

antioxidants