glucose metabolism glycolysis: 2 nadh, 2 atp (net) pre-tca cycle: 2 nadh tca cycle: 6 nadh, 2 fadh...
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![Page 1: Glucose metabolism Glycolysis: 2 NADH, 2 ATP (net) Pre-TCA cycle: 2 NADH TCA cycle: 6 NADH, 2 FADH 2, 2 A/GTP Some ATP Big bonus: NADH, FADH 2 → REDUCING](https://reader036.vdocuments.site/reader036/viewer/2022081504/56649f135503460f94c27a04/html5/thumbnails/1.jpg)
Glucose metabolism
• Glycolysis: 2 NADH, 2 ATP (net)
• Pre-TCA cycle: 2 NADH
• TCA cycle: 6 NADH, 2 FADH2, 2 A/GTP
Some ATPBig bonus: NADH, FADH2 →
REDUCING POWER
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Energy harvest by respiration
• Carbon-carbon bonds: chemical energy
• NADH, FADH2: energy of oxidation
• Proton gradient: potential energy
• ATP synthesis: useable chemical energy
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Reducing power/Energy of oxidation
• Not very user-friendly
• How to harvest the energy?
• Electron transport chain– Change energy of oxidation into potential
energy (H+ gradient)– Change potential energy into chemical energy
(F1Fo ATP synthase)
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What is energy of oxidation?• Reducing potentials:
NAD+ + H+ + 2e- → NADH E'° ~ -0.414V
ubiquinone + 2H+ + 2e- → ubiquinol E'° ~ +0.045
Electrons (e-) flow spontaneously from NADH to ubiquinone
NADHubiquinone
(reduced form)(oxidized form)
NADH IS A STRONGER REDUCING AGENT THAN UBIQUINOL
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Cataloging the red/ox reactionTransfer of e- from NADH to ubiquinone
NADH → NAD+ + H+ + 2e-
ubiquinone + 2H+ + 2e- → ubiquinol
NADH + ubiquinone + H+ → ubiquinol + NAD+
E'° (V)
+0.414
+0.045
+0.459
*extra energy*not yet useableE'° > 0 ~ G'° < 0
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Electrons are passed among redox carriers
NADH→NAD+
FMN (↔FMNH2)
Fe-S Cluster
Ubiquinone (coenzyme Q)
Cytochrome C
O2→H2O
REDUCINGSTRENGTH
Couple energetically favorable reactionsto energetically unfavorable reactionsOverall -G
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MATRIXGeneration of NADH
INTERMEMBRANESPACE
Redox energy is transformed into potential energy
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MATRIX
INTERMEMBRANESPACE
High pH (lower [H+])Electrically negative
Low pH (higher [H+])Electrically positive
Flow of H+ into the matrixIs energetically favorable 1. Input energy to move H+ out 2. Harvest energy
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Mitochondria actually look like the cartoons
http://www.tmd.ac.jp/http://faculty.ircc.edu
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Redox energy is transformed into potential energy
Establishment of a chemical and electric gradient across the inner membrane
F1Fo ATP synthaseTransforms potentialEnergy into useableChemical energy
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Electron transport between electron carriers occurs in protein complexes within the inner
membrane
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Complex I• NADH: Ubiquinone
oxidoreductase – 850kDa, 43 subunits– Converts NADH to NAD+
– e- transferred through complex• FMN, Fe-S clusters
– 4 protons are ‘pumped’ from the matrix into the intermembrane space
– Reduces ubiquinone (Q) to ubiquinol (QH2)
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Ubiquinol (reduced coenzyme Q)
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Complex III• Coenzyme Q:cytochrome c
oxidoreductase– 250 kDa– 11 subunits– 2 coQ oxidized, one CytC
reduced– e- carriers:
• Hemes, Fe-S clusters– Net 4 H+ pumped to
intermembrane space
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Complex III, cont.
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Cytochrome C
• Heme group carries electrons
• Loosely associated with membrane
• Shuttles e- from complex III to IV
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Complex IV• Cytochrome C oxidase
– 160 kDa– 13 subunits– Reduces oxygen
– ½ O2 + 2H+ + 2e- → H2O
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Complex II (Use of FADH2)• Succinate dehydrogenase
– Membrane-bound enzyme in the TCA cycle
– 140 kDa– 4 subunits– FAD, Fe-S clusters carry
electrons– e- transferred ubiquinone(Q)
– QH2 carries e- to complex 3
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Electron transport
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Overall reaction starting with 2 e- from one NADH
NADH + H+ + ½ O2 → NAD+ + H2O
G'° ~ -220 kJ/mol (of NADH)
-highly favorable-coupled to transport of ~10 H+
against a chemical/electrical gradient
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Oxidative phosphorylation
• Involves reduction of O2 to H2O by NADH and FADH2
• ATP synthesized through e- transfers
• Inner mitochondrial membrane– Embedded protein complexes
• Succinate dehydrogenase
– Impermeable to most small molecules (and H+)
• Creation of electrochemical gradients
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ATP generation• 2 NADH, 2 ATP from glycolysis (glucose)• 1 NADH from pre-TCA (each pyruvate)
• 3 NADH, FADH2 from TCA (each acetyl CoA)– 2 e- from NADH yields 2.5 ATP*
– 2 e- from FADH2 yields 1.5 ATP