Download OXIDATIVE PHOSPHORYLATION

OXIDATIVE
PHOSPHORYLATION
9/25/07
ATP _ Universal Carrier of Free Energy
Provides Energy for:
_ Mechanical
_ Chemical
Work
_ Ionic
Role of ATP in Metabolism
Know this structure
It is the most important molecule in biochemistry.
The Concept
Energy rich molecules donate
electrons to specific coenzymes
to form energy-rich reduced
coenzymes
1 pair of electrons is donated
per each reduced coenzyme
H2 = H + H
H = 1 electron + 1 proton
:H¯ = 2 electrons + 1 proton
(Hydride ion)
+
+
H = 1 proton
These electrons are
donated to the electron
transport chain to form
ATP
Electrochemical gradient
Oxidized
Reduced
Carriers and transport systems
are used to move ions and
molecules across this membrane
Glycolysis
Cytoplasm
• Membrane convoluted or folded
= ↑ Surface Area
(Cristae)
Electron Transport
Contains the ATP Synthetase
complex
• Inner mitochondrial membrane
• Is the final common pathway
by which electrons from food
molecules are used to make
ATP and molecular oxygen
acts as the final acceptor
of the electrons
ATP Synthetase complex
50% protein
NADH
Dehydrogenase
Final acceptor of e-s is
molecular oxygen
Citric acid cycle
2 e¯
Citric acid cycle
2 e¯
Cytochrome oxidase
(Iron + copper)
Complex V contains ATP Sythase
• Series of Oxidation/Reduction reactions
Electron transport chain ▬ 3 components
• Flavoprotein ▬ NADH Dehydrogenase
• CoQ (Quinone) ▬ Ubiquinone
• Cytochromes ▬ Heme group ▬ Iron
Ferric (Fe3+)
▬ Ferrous (Fe2+)
▬
Cyanide
Each one of these inhibitors will completely stop electron transport
and thus all ATP production
Three Main Tenets of the Mitchell Theory
ATP Synthase
FAD+
FADH2
This dissipates
gradient
Blocked by atractyoside
(Plant toxin)
ATP
Oligomycin
blocks
Lower pH
pH gradient
More protons
Electrical
gradient
ADP
ATP
Cytoplasm
1 NADH = 3 ATP
1 FADH2 = 2 ATP
Chemiosmotic Hypothesis of Electron Transport coupled to ADP Phosphorylation
▬ “Mitchell Hypothesis”
Features:
• Protons transported from the matrix to the inner mitochondrial space results
in an electric gradient and a pH gradient
• As the protons flow through the membrane channel back into the matrix
they drive ATP synthesis
Occurs with energy utilized by ATP synthase
This proton transport couples electron transport to oxidative phosphorylation
Uncoupling of Oxidative Phosphorylation
O2
Electron Transport
ADP
ADP
Electron transport coupled to
phosphorylation of ADP  ATP
ADP
H2O
ATP
ATP
ATP
Introduced in 1932 as weight reduction drug
= Fatal hyperthermia
+ Dinitrophenol (DNP) breaks down proton gradient
High doses of aspirin ▬ results in fever
O2
Electron transport continues
Electron Transport
No ADP phosphorylation
Energy dissipated as heat
H2O
HEAT
Brown adipose tissue creates heat by thermogenesis
Thermogenin = uncoupling protein ▬ UCP1
The energy is given off
as heat
Mechanism is to
↑ FA oxidation which
uncouples oxidation
phosphorylation
Breaks down proton gradient
Inherited Diseases of Oxidative Phosphorylation
LIBER’S HEREDITARY OPTIC NEUROPATHY
Bilateral loss of central vision occurs because of
Neuroretinal degeneration
Mutation in mitochondrial DNA
Mitochondrial DNA is maternally inherited
because all mitochondria come from the mother
None come from the sperm because none from
sperm enter the egg during fertilization
Some mitochondrial myopathies caused by
mutations in mtDNA
13 of the ~100 proteins in the mitochondrion are
coded for by mtDNA
Has mutation rate > 10x that of nuclear DNA
Glycerophosphate shuttle
2 ATP for each NADH transported into mitochondrion
from the cytoplasm
Malate-Aspartate shuttle
3 ATP for each NADH
1
2
3
6
4
7
5
2 Shuttle systems to bring cytosolic NADH into
mitochondria for oxidative phosphorylation
1) Glycerophosphate shuttle = 36 ATP
8
2) Malate-aspartate shuttle = 38 ATP
Count ATPs: Anerobic glycolysis = 2
Glycolysis + CAC + oxidative phosphorylation = 38
NADH
FADH2
ATP
1
Glycolysis
2
Glycolysis (G-3-P  1,3,BisP)
2
6
3
Pyruvate  Acetyl CoA
2
6
4, 5, 6
CAC
6
18
7
CAC-FADH2
8
CAC – substrate level ATP
Total
2
2
4
2
38
Revolves at 100 Hz (revolutions/s)
This is sufficient to produce a turnover of
The weight of our body of ATP each day!
ATP synthase:
• 2 Domains
F1
F0
• Rotates in 120° stages
• 100 Hz one complete revolution = 3 ATP
• Need 10 H+
.
. . 1 ATP = 3.3 H+