Glucose metabolism
• Glycolysis: 2 NADH, 2 ATP (net)
• Pre-TCA cycle: 2 NADH
• TCA cycle: 6 NADH, 2 FADH2, 2 A/GTP
Some ATP
Big bonus: NADH, FADH2 →
REDUCING POWER
Energy harvest by respiration
• Carbon-carbon bonds: chemical energy
• NADH, FADH2:
energy of oxidation
• Proton gradient:
potential energy
• ATP synthesis:
useable chemical
energy
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)
What is energy of oxidation?
• Reducing potentials:
NAD+ + H+ + 2e- → NADH
E'° ~ -0.414V
ubiquinone + 2H+ + 2e- → ubiquinol E'° ~ +0.045
NADH IS A STRONGER REDUCING AGENT THAN UBIQUINOL
Electrons (e-) flow spontaneously from NADH to
ubiquinone
NADH
(reduced form)
ubiquinone
(oxidized form)
Cataloging the red/ox reaction
Transfer of e- from NADH to ubiquinone
E'° (V)
NADH → NAD+ + H+ + 2e- +0.414
ubiquinone + 2H+ + 2e- → ubiquinol
+0.045
NADH + ubiquinone + H+ → ubiquinol + NAD+ +0.459
*extra energy*
DE'° > 0 ~ DG'° < 0
not yet useable
Electrons are passed among
REDUCING
redox carriers
STRENGTH
NADH→NAD+
FMN (↔FMNH2)
Fe-S Cluster
Ubiquinone (coenzyme Q)
Cytochrome C
Couple energetically favorable reactions
to energetically unfavorable reactions
O2→H2O
Overall -DG
Redox energy is transformed
into potential energy
MATRIX
Generation of NADH
INTERMEMBRANE
SPACE
INTERMEMBRANE
SPACE
Low pH (higher [H+])
Electrically positive
Flow of H+ into the matrix
Is energetically favorable
1. Input energy to
move H+ out
2. Harvest energy
MATRIX
High pH (lower [H+])
Electrically negative
Mitochondria actually look like
the cartoons
http://faculty.ircc.edu
http://www.tmd.ac.jp/
Redox energy is transformed into
potential energy
Establishment of a chemical and electric gradient
across the inner membrane
F1Fo ATP synthase
Transforms potential
Energy into useable
Chemical energy
Electron transport between electron carriers
occurs in protein complexes within the inner
membrane
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)
Ubiquinol
(reduced coenzyme Q)
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
Complex III, cont.
Cytochrome C
• Heme group carries
electrons
• Loosely associated
with membrane
• Shuttles e- from
complex III to IV
Complex IV
• Cytochrome C oxidase
–
–
–
–
160 kDa
13 subunits
Reduces oxygen
½ O2 + 2H+ + 2e- → H2O
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
Electron transport
Overall reaction starting with
2 e- from one NADH
NADH + H+ + ½ O2 → NAD+ + H2O
DG'° ~ -220 kJ/mol (of NADH)
-highly favorable
-coupled to transport of ~10 H+
against a chemical/electrical gradient
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
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