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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.
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We have made small amounts of ATP so far
The main product is the 24 H+ (24 e-) that are produced
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Mitochondrion
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Cristae are not necessarily uniform structures
Cristae are not necessarily uniform structures. They can vary greatly, restricting local ion movement, creating a large pH gradient.
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How does NADH get into Matrix
Aspartate-Malate shuttle Glycerophosphate shuttle Insect muscle Same power to weight ratio as a small car engine
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Transport of Materials
ATP/ADP Translocator One for one Charge problems Phosphate Symporter Phosphate and H+ Both driven by pH gradient
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Efficiency of ETC Δε°’= -0.315 V Δε°’= 0.815 V
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%
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Inhibitors of ETC Complex I Complex IV Complex III
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10 in humans
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Complex I
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Rhodopsin – Model Proton Pump
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Complex II Complex I and Complex II are not sequential, but accept electrons from different sources. Complex I – NADH Complex II - succinate
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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.
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Q cycle Q-cycle involves two cycles
Proton pumping of complex III is different from complex I or II
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Complex IV Requires 4 electrons Contains Cu and Fe
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Reaction center requires 4 electrons at once
Fe(II)-Cu(I) contributes only 3 electrons Fourth electron comes from Y244 forming a tyrosyl radical
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Chemiosmotic Theory 1961 Peter Mitchell Observations
OP needs intact inner mitochondrial membrane Inner MM impermeable to H+, OH-, K+, Cl- ET sends H+ out Compounds that increase permeability of the MM inhibit ATP synthesis
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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 kJ/mol It takes 2-3 H+ ions moving with the gradient to provide the energy to synthesize 1 ATP
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ATPase portion Membrane portion
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F1 region of ATP synthase
Only beta subunits can catalyze ATP synthesis
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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
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pH=8 pH=5 Only the c ring moves, not alpha and beta parts Arg210
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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
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Uncoupling Leads to Generation of Heat
Diet pill?
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