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1
SURVEY OF BIOCHEMISTRYElectron Transport and
Oxidative Phosphorylation
2
Redox Centers
3
The Mitochondrion
Zoom in on the cristae:
~2000 per cell
4
How does electron transfer work?
NADH binds to Complex I on the matrix side
of the membrane
5
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
6
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:
7
Fe-S Clusters in Complex I
Complex I contains Fe-S clusters as cofactors
8
Coenzyme Q (Ubiquinone)
Electrons pass from Fe-Sclusters to a “mobile”
electron carrier cofactor called Coenzyme Q
9
Electron Transfer with CoQ
Coenzyme Q initially binds to Complex I to pick up 2 e- from the Fe-S clusters in Complex I
10
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
11
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
12
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
13
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.
14
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)
15
Complex III and Complex IV
Cytochrome bc1
O2 + 4 H+ 2H2O
Cytochrome c oxidase
How does ATP get made?
16
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.
17
Complex V: ATP Synthase
F1F0 ATPase
F0 - water insolublew/ 8 types of subunits
F1 - water solubleperipheral membraneprotein w/ 5 types of
subunits
18
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
19
Overview of Electron Transport
Notice theseinhibitors of
electron transport!
20
Coordinated Control of Glycolysis and the TCA Cycle
21
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!
22
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
23
Superoxide Dismutase (SOD)
• An inherent antioxidant enzyme
2O2-• + 2H+ O2 + H2O2
Catalase
SOD
2H2O2
2 H2O + O2
Otherpotential
antioxidants