Fundamentals of
Biochemistry
Third Edition
Donald Voet • Judith G. Voet •
Charlotte W. Pratt
Chapter 18
Electron Transport and Oxidative Phosphorylation
Copyright © 2008 by John Wiley & Sons, Inc.
We have made small amounts
of ATP so far
The main product is the 24 H+
(24 e-) that are produced
Mitochondrion
Cristae are not
necessarily uniform
structures. They
can vary greatly,
restricting local ion
movement, creating
a large pH gradient.
How does NADH get into Matrix
• Aspartate-Malate
shuttle
• Glycerophosphate
shuttle
– Insect muscle
– Same power to
weight ratio as a
small car engine
Transport of Materials
• ATP/ADP
– Translocator
– One for one
– Charge problems
• Phosphate
– Symporter
– Phosphate and H+
• Both driven by pH
gradient
Efficiency of ETC



NAD  H  2e  NADH
0.5O2  2 H   2e   H 2O
Δε°’= -0.315 V
Δε°’= 0.815 V
0.5O2  NADH  H   H 2O  NAD
  '  0.815V   0.315V   1.130V
G  '  n  '
G  '  218kJ  m ol1
If 1 NADH makes 2.5 ATP and it takes 30.5 kJ/mol to make 1 ATP
Efficiency of ATP synthesis is ~100kJ/mole / 218kJ/mol = 35%
Inhibitors of ETC
Complex I
Complex IV
Complex III
10 in humans
Complex I
Rhodopsin – Model Proton Pump
Complex II
Complex I and
Complex II are not
sequential, but accept
electrons from
different sources.
Complex I – NADH
Complex II - succinate
Complex III
Pass electrons from CoQ
to cytochrome c
Electrons in Complex III
must go from a 2 e- carrier
(CoQH2) to a 1 e- carrier,
cytochrome c.
Q cycle
Q-cycle involves two cycles
Proton pumping of complex III
is different from complex I or II
Complex IV
Requires 4 electrons
Contains Cu and Fe
Reaction center requires
4 electrons at once
Fe(II)-Cu(I) contributes
only 3 electrons
Fourth electron comes
from Y244 forming a
tyrosyl radical
• Chemiosmotic Theory
– 1961 Peter Mitchell
– Observations
•
•
•
•
OP needs intact inner mitochondrial membrane
Inner MM impermeable to H+, OH-, K+, ClET sends H+ out
Compounds that increase permeability of the MM
inhibit ATP synthesis
Harnessing the Energy
• The free energy of sending a proton against
the gradient is approximately 22 kJ/mol
• The free energy required to synthesize one
ATP is approximately 40-50 kJ/mol
• It takes 2-3 H+ ions moving with the
gradient to provide the energy to synthesize
1 ATP
ATPase portion
Membrane portion
F1 region of ATP synthase
Only beta subunits can
catalyze ATP synthesis
ATP synthesis
• ADP + Pi bind to L site
• Free energy drives conformational change
– Only T site catalyzes ATP synthesis
• ATP is release following next
conformational change
pH=8
pH=5
Only the c ring moves,
not alpha and beta parts
Arg210
PO Ratios
• ATP synthesized(P)/Oxygen reduce(O)
– 2 electrons through Complex I, III, IV result in
10 protons which rotates the c subunits one
revolution thereby synthesizing 3 ATP
– 2 electrons from FADH2 enter complex II and
result in 6 protons or ~2ATP
– Estimates for glucose
•
•
•
•
•
2.5 ATP/NADH; 10 NADH/glucose
1.5 ATP/FADH2; 2 FADH2/glucose
2 ATP/glucose from glycolysis
2 ATP/glucose from citric acid cycle
Total = 32 ATP/glucose
Uncoupling Leads to Generation of
Heat
Diet pill?