Electron Transport
and
Oxidative
Phosphorylation
Lesson Learning Outcomes
Upon completion of this lecture, students
should be able to:
understand the electron transport chain
understand the oxidative phosphorylation
Electron Transport Chain
Carried out by four closely related multi subunit
membrane-bound complexes and two electron
carriers, coenzyme Q and cytochrome c
in a series of oxidation-reduction reactions,
electrons from FADH2 and NADH are
transferred from one complex to the next until
they reach O2
O2 is reduced to H2O
O2 + 4H+ + 4e-
2H2 O
as a result of electron transport, protons are
pumped across the inner membrane to the
intermembrane space
Electron Transport Chain
Proton gradient across inner mitochondrial membrane
Electron Transport Chain
the proton gradient establishes a
voltage gradient
the proton and voltage gradients
together provide the
mechanism to
couple
electron
transport
with
phosphorylation of ADP
ADP + Pi
ATP + H2 O
Complex I
NADH-CoQ oxidoreductase
electrons are passed from NADH to coenzyme Q through a series of reaction
H3 C
H3 C
2H+ + 2e-
NH
O
N
N
CH2
(CHOH) 3
CH2 OPO32 -
Flavin mononucleotide
(FMN)
H3 C
H3 C
H
N
O
NH
O
N
N
CH2 H
(CHOH) 3
CH2 OPO32-
Dihydroflavin mononucleotide
(FMNH2 )
Complex I
electrons are then passed to the ironsulfur clusters
finally,
electrons
are
passed
to
coenzyme Q (also called ubiquinone)
O
CH3 O
CH3
CH3 O
(CH2 CH=CCH2 ) n H + 2H+ + 2e-
CH3
O
Coenzyme Q
(oxidized form)
reduction
oxidation
OH
CH3 O
CH3
CH3 O
(CH2 CH=CCH2 ) n H
CH3
OH
Coenzyme QH2
(reduced form)
Complex I
the overall equation for the reaction of
complex I is
NADH + H+ + E-FMN
E-FMNH2 + 2Fe-S( ox)
Fe-S( red) + CoQ + 2H+
NADH + H+ + CoQ
NAD+ + E-FMNH2
E-FMN + 2Fe-S( red) + 2H+
Fe-S( ox) + CoQH2
NAD+ + CoQH2
G' = -81 kJmol-1
this transfer of electrons is strongly
and +isH sufficient
to drive
the
-1
+ Pi
ADPexergonic
ATP
O
G'
=
+30.5
kJmol
2
phosphorylation of ADP
Complex II
Succinate-coenzyme Q oxidoreductase
COOCH2
CH2
H
+ E-FAD
COOSuccinate
E-FADH2 + CoQ
Succinate + CoQ
OOC
C
C
COO+ E-FADH2
H
Fumarate
E-FAD + CoQH2
Fumarate + CoQH2
G' = -13.5 kJmol-1
the overall reaction is exergonic, but not enough
to drive ATP production
no H+ is pumped out of the matrix during this step
Redox Forms of CoQ
O
CH3 O
CH3
CH3 O
O
Coenzyme Q
e-
e-
O
CH3 O
CH3
CH3 O
OCoenzyme Q2H+ + e-
2H+ + eOH
CH3 O
CH3
CH3 O
OH
Coenzyme QH2
Complex III
CoQH2-cytochrome c
oxidoreductase
+ 2Cyt c[Fe( III)]
CoQH2
CoQ + 2Cyt c[Fe( II)] + 2H+
G' = -34.2 kJmol-1
this decrease in free energy is sufficient to
drive the phosphorylation of ADP to ATP
(DG0 = + 30.5 kJmol-1)
Complex IV
Cytochrome oxidase:
2Cyt c[Fe( II)] + 2H+ + 1 O2
2
2Cyt c[Fe( III)] + H2 O
G' = -110 kJmol-1
complex IV contains cytochrome a,
cytochrome a3, and Cu(II), which are
also involved in the electron transport
complex IV is the link with molecular
oxygen +
1
+
NADH + H + 2 O2
NAD
+ H2 O
Electron Transport Chain
Coupling Oxidation and
Phosphorylation
the energy-releasing oxidations give rise
to proton pumping and a pH gradient
across the inner mitochondrial membrane
in
addition,
differences
in
the
concentration
of
ions
across
the
membrane generates a voltage gradient
a
coupling
process
converts
the
electrochemical potential to the chemical
energy of ATP
the coupling factor is ATP synthase, a
complex protein oligomer, separate from
the electron transport complexes
ATP Synthase
Coupling Ox and Phos
P/O ratio: gives the number of moles of Pi
consumed in phosphorylation to the number
of moles of oxygen atoms consumed in
oxidation
Phosphorylation (P)
ADP + Pi
ATP + H2 O
Oxidation (O)
+
1/ 2O2 + 2H + 2e
H2 O
P/O = 2.5 or 3.0 when NADH is oxidized (3 ATP)
P/O = 1.5 or 2.0 when FADH2 is oxidized (2ATP)
Mechanism of Ox/Phos
The mechanism by which the proton gradient
leads to the production of ATP depends on ion
channels through the inner mitochondrial
membrane.
protons flow back into the matrix through
channels
the flow of protons is accompanied by
formation of ATP
the details of how phosphorylation takes place
as a result of the linkage to the proton
gradient are not explicitly specified by this
mechanism
The overall effect of electron transport reaction series is to
move protons out of the matrix into the intermembrane
space, creating a difference in pH across the membrane.
Formation of ATP accompanies the flow of
protons back into the mitochondrial matrix.
Shuttle Mechanisms
Shuttle mechanisms: transport metabolites
between mitochondria and cytosol
Glycerol phosphate shuttle:
Glycolysis in the cytosol produces NADH
NADH does not cross the mitochondrial
membrane, but glycerol phosphate and
dihydroxyacetone phosphate do
Through the glycerol phosphate shuttle,
1.5 ATP are produced in the mitochondria
for each cytosolic NADH
Has been found in insect flight muscle,
mammalian muscle and brain
The Glycerol-Phosphate
Shuttle
The Malate-Aspartate Shuttle
The Malate-Aspartate Shuttle:
Has been found in mammalian kidney,
liver, and heart
Malate
crosses
the
mitochondrial
membrane, while oxaloacetate cannot
The transfer of electrons from NADH in the
cytosol produces NADH in the mitochondria
In the malate-aspartate shuttle, 2.5
mitochondrial ATP are produced for each
cytosolic NADH
The Malate-Aspartate
Shuttle
Summary
Shuttle mechanisms transfer electrons, but
not NADH, from the cytosol across the
mitochondrial membrane
In the malate-aspartate shuttle, 2.5
molecules of ATP are produced for each
molecule of cytosolic NADH, rather than
1.5 ATP in the glycerol-phosphate shuttle,
a point that affects the overall yield of ATP
in these tissues
The ATP Yield from Complete
Oxidation of Glucose
In the complete oxidation of glucose, a
total of 30 or 32 molecules of ATP are
produced for each molecule of glucose,
depending on the shuttle mechanism
End of lecture