OXIDATIVE PHOSPHORYLATION 9/25/07. ATP _ Universal Carrier of Free Energy _ Chemical _ Ionic...
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Transcript of OXIDATIVE PHOSPHORYLATION 9/25/07. ATP _ Universal Carrier of Free Energy _ Chemical _ Ionic...
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OXIDATIVE PHOSPHORYLATION
9/25/07
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ATP _ Universal Carrier of Free Energy
_ Chemical_ Ionic
Provides Energy for:_ Mechanical
Work
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Role of ATP in Metabolism
Know this structure
It is the most important molecule in biochemistry.
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The Concept
Energy rich molecules donateelectrons to specific coenzymesto form energy-rich reducedcoenzymes
1 pair of electrons is donatedper each reduced coenzyme
H2 = H + H
H = 1 electron + 1 proton
:H¯ = 2 electrons + 1 proton
(Hydride ion)+
H+ = 1 proton
These electrons aredonated to the electrontransport chain to formATP
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Electrochemical gradient
Oxidized Reduced
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Glycolysis
Cytoplasm
Electron Transport
• 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
Carriers and transport systemsare used to move ions andmolecules across this membrane
• Membrane convoluted or folded
= ↑ Surface Area
(Cristae)
Contains the ATP Synthetasecomplex
ATP Synthetase complex
50% protein
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NADHDehydrogenase
Citric acid cycle
2 e¯
Citric acid cycle 2 e¯
Final acceptor of e-s is molecular oxygen
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+)
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Each one of these inhibitors will completely stop electron transportand thus all ATP production
Cyanide
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Three Main Tenets of the Mitchell Theory
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ATP Synthase
This dissipatesgradient
Blocked by atractyoside(Plant toxin)
FADH2
FAD+
Lower pH
pH gradient
Oligomycinblocks
ADP
ATP
ATP
More protons
Electricalgradient
1 NADH = 3 ATP1 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 synthaseThis proton transport couples electron transport to oxidative phosphorylation
Cytoplasm
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Uncoupling of Oxidative Phosphorylation
Electron Transport
ADP
ATP
ADP
ATP
ADP
ATP
O2
H2O
Electron transport coupled tophosphorylation of ADP ATP
Electron Transport
O2
H2O
+ Dinitrophenol (DNP) breaks down proton gradientHigh doses of aspirin ▬ results in fever
Introduced in 1932 as weight reduction drug= Fatal hyperthermia
Electron transport continues
No ADP phosphorylation
Energy dissipated as heat
HEAT
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Brown adipose tissue creates heat by thermogenesis
Thermogenin = uncoupling protein ▬ UCP1
The energy is given offas heat
Mechanism is to↑ FA oxidation whichuncouples oxidationphosphorylation
Breaks down proton gradient
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Inherited Diseases of Oxidative Phosphorylation
LIBER’S HEREDITARY OPTIC NEUROPATHY
Bilateral loss of central vision occurs because ofNeuroretinal degeneration
Mutation in mitochondrial DNA
Mitochondrial DNA is maternally inheritedbecause all mitochondria come from the mother
None come from the sperm because none from sperm enter the egg during fertilization
Some mitochondrial myopathies caused bymutations in mtDNA
13 of the ~100 proteins in the mitochondrion arecoded for by mtDNA
Has mutation rate > 10x that of nuclear DNA
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Malate-Aspartate shuttle
3 ATP for each NADH
Glycerophosphate shuttle
2 ATP for each NADH transported into mitochondrionfrom the cytoplasm
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1
2 3
4
6
75
8
2 Shuttle systems to bring cytosolic NADH intomitochondria for oxidative phosphorylation
1) Glycerophosphate shuttle = 36 ATP
2) Malate-aspartate shuttle = 38 ATP
Count ATPs: Anerobic glycolysis = 2 Glycolysis + CAC + oxidative phosphorylation = 38
NADH FADH2 ATP
1 Glycolysis 2
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 2 4
8 CAC – substrate level ATP 2
Total 38
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Revolves at 100 Hz (revolutions/s)
This is sufficient to produce a turnover ofThe 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+...
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