Download LECT 12 Electrontransp

The final piece of the puzzle
Electron transport
and
Oxidative phosphorylation
Take a deep breath and push on
Major Energy
Pathways
Glycolysis
Anaerobic
Lactate
pyruvate
Glucose
Galactose
Fructose
Mannose
Fatty Acids
Aerobic
1 FADH2
Acetyl-CoA
Amino Acids
Krebs Cycle
3 NADH
O2
Oxidative phosphorylation
H2
Electron Transport and Oxidative Phosphorylation
1. The absolute heart of aerobic metabolism
2. Three Functional Phases
Electron transfer from NADH, FADH2 to O2
Energy preserved as a proton gradient
Proton gradient energy makes ATP
We are making ATP from ADP and Pi by tapping
the oxidative energy generated in the transfer of
electrons to O2
Anatomy of Mitochondria
Mitochondria are composed of a dual membrane system:
Outer: Porous to all molecules < 10 kDa
Inner: Transporter-dependent transport
Inner Membrane Transport in Mitochondria
Densely packed with specific membrane transporters and
the electron-transporting complexes
Strategies p219
Electron Transport
The successive passage of electrons through a series of
membrane complexes to Oxygen.
NADH
FMN
Complex I
CoQ
Cyt b
Cyt c1
Complex III
Cyt c
Cyt a+a3
O2
Complex IV
Table 1: Cytochromes in the Electron Transport System
1.
2.
3.
4.
5.
6.
7.
Cytochrome b562 also called bH
Cytochrome b566 also called bL
Cytochrome b560
Cytochrome c1
Cytochrome c
Cytochrome a
Cytochrome a3
Complex III
Complex III
Complex II
Complex III
Mobile
Complex IV
Complex IV
Fe2+/Fe3+
Fe2+/Fe3+
Fe2+/Fe3+
Fe2+/Fe3+
Fe2+/Fe3+
Fe2+/Fe3+ Cu+/Cu2+
Fe2+/Fe3+ Cu+/Cu2+
Transport Mechanism
A bucket-brigade
..
NADH
NAD+
..
FMN CoQH2
..
..
Cyt b Cyt c1
(Fe3+) (Fe2+)
FMNH2 CoQ Cyt b
(Fe2+)
..
..
Reduced
-0.32 volts
Cyt c1
(Fe3+)
Cyt
Cyt c a+a3
(Fe3+) (Fe2+)
Cyt c Cyt
(Fe2+) a+a3
.. (Fe3+)
O2
H2O
..
Oxidized
+ 0.82 volts
Electron Transport Complexes
• Membranes bound heme proteins or
“cytochromes”
• Iron-Sulfur proteins..high reducing potential
• Mobile electron carriers
– Coenzyme Q
– Cytochrome c
Electron Transport
NADH
-0.32
Reductive Energy
Complex I
CoQ H2
Complex II
Complex III Cyto C Fe2+
FADH2
O2
Complex IV
+0.82
H2O
Oxidative Energy
Iron-Sulfur Centers
Cys
Cys
Cys
S
S
Cys
Fe
s
s
2-
S
S
Cys
S
Fe
Fe
S
Cys
S
S22Fe-2S
Fe-S
Cys
Cys
Coenzyme Q
O.
O
CH3
H3CO
H3CO
O
Oxidized CoQ
(no electrons)
CH3
(CH2= C CH2)n H
isoprenoid units
n =6-10
OH
H3CO
CH3
H3CO
CH3
H3CO
R
H3CO
R
OH
CoQH.
Semiquinone
Form
(one electron)
OH
CoQH2
Quinol Form
(2 electrons)
NADH
Mobile
I
III
CoQ-cyto c
Reductase
NADH-CoQ
Reductase
FMN
FeS
CoQ
II
Cyt b562
Cyt b566
FeS
Cyt c1
Succinate-CoQ
Reductase
FAD
FeS
Cyt b560
Succinate
Fumarate
Cyto c
IV
Cu2+
Cyt a
Cyt a3
Electron Transport
Complexes
O2
Energy Time
Textbook p372
How does the energy of oxidation translate
into free energy?
DGo’ = –nFDEo’
F = Faraday’s constant = 96,500 J/mol x volt
n = Number of electrons
Eo’ = Standard Reduction Potential at pH 7
DE = DEo’ + 0.06 log
[electron acceptor]
[electron donor]
Nernst Equation for one electron transfer
Determines DE under non-standard state conditions
DE = DEo’ + 0.06 log
pH = pKa + log
[electron acceptor]
[electron donor]
[proton acceptor]
[proton donor]
Acid/Base
Redox
pH
DE (reduction potential)
pKa
DEo’ (standard reduction
potential)
Proton Acceptor (base)
Electron acceptor (oxidant)
Proton Donor (acid)
Electron donor (reductant)
Acceptors
(Oxidants)
e-
Donors
(Reductants)
DEo’= Eo’ acceptor - Eo’ donor
NAD+ + H2O
NADH + H+ + 1/2 O2
NAD+ + 2e + 2H+
1/2 O2 + 2e + 2H+
NADH + H+
H2 O
Eo’
–0.32 volts
+0.82 volts
To Arrive at equation:
Top reduces bottom
NADH + H+
1/2
NAD+ +2e + 2H+
O2 + 2e + 2H+
NADH + H+ +
Coulomb/mol
1/2
O2
DGo’ = –nFDEo’
H2O
+0.32 volts
+0.82 volts
NAD+ + H2O +1.14 volts
J/Coulomb
DGo’ = –220 kJ/mol
Shuttles
Problem: Cytosolic NADH cannot penetrate
the mitochondria
Solution: Pass the electrons to something that can
penetrate the mitochondria membrane
Two Shuttles
Insect brain and flight muscle
Glycerol-PO4
FADH2
2 ATP per NADHc
Malate-aspartate
NADH
3 ATP per NADHc
Mammalian muscle and liver
Glycerol-PO4
Shuttle
Cytosol
CH2OH
DHAP
:
NADH
NAD+
CH2OH
:
HO-C-H
C=O
CH2OP
Glycerol-PO4
CH2OP
Membrane
transporter
CH2OH
Flavoprotein
dehydrogenase
C=O
CH2OP
FADH2
2ATP
FAD
:
CH2OH
:
HO-C-H
CH2OP
Mitochondria
Malate-Aspartate
P457
COO
+
COO NADH
Aminotransferase
H3N-C-H
COO
HO-C-H
C=O
CH2
Malate
dehydrogenase
CH2
a-Kg
COO
NAD+
CH2
COO
GluCOO
OAA
L-malate
Cytosol
COO
+
a-Kg
Mitochondria
Glu COO
H3N-C-H
C=O
CH2
COO
Asp
Aminotransferase
CH2
Malate
dehydrogenase
COO
HO-C-H
NADH NAD+
COO 3ATP
CH2
COO