Oxidative Phosphorylation / ETC Flashcards
What physical characteristic allows the H+ gradient to be created
The IMM in immpermeable to charged ions
The 3 main electron carriers in the ETC
- Cytochromes
- Iron sulfur proteins
- Coenzyme Q (aka ubiquinone)
Cytocromes
Heme backbone
3 cytochrome structures
- A
- B (heme cytochrome)
- C
The iron on the heme cycles between reduced and oxidized state
Iron sulfur proteins
Iron = accepting/releasing e-
Iron is caged between the sulfurs (either free or from cysteine)
Coenzyme Q (ubiquinone)
Can accept 2e- from NADH
Go through a semiuinone radical
CoQ = greasy hydrophobic tail…therefore it is embedded in the IMM
—> makes it a mobile carrier…transfers electrons from one carrier to another
NADH dehydrogenase complex
‘Complex I’
Removes e- from NADH
Entry point for NADH
Main carrier = iron/sulfur protein
Pumps out 4H+
Succinate dehydrogenase complex
‘Complex II’
FADH2 —> FAD
Entry point for FADH2
Main carrier = iron/sulfur protein
NO H+ pumped out
Ubiquinone cytochrome C oxidoreductase complex
‘Complex III’
Receives electrons from complex 1 or 2…becomes reduced
Main carrier = heme and iron/sulfur proteins
4H+ pumped out
Cytochrome C complex
In between complex 3 and 4
Carrier electrons from 3 —> 4 one electron at a time until complex 4 has 4 electrons
NO H+ pumped out
Cytochrome oxidase complex
‘Complex IV’
Transfers electrons from cytochrome C —> O2
Main carriers = heme and 2 copper groups
Pumps 2H+ out
Electron entry points
Electrons enter and are transferred to CoQ…
A. NADH = complex I
B. FADH2 = complex II
C. Glycerol-3P dehydrogenase in the IMM
D. Fatty acid oxidation
ATP Synthase complex
Converts chemical gradient of H+ —> ATP ultimately
2 parts:
- Head (F1) = where ATP synthesis takes place
- round base (F0)
Bottom = 10 subunits that twist Shaft = epsilon and gamma connect rotor to head groups...
ATP synthase mechanism
As protons move down the gradient created by the ETC…
The circular base in the membrane turns…
As the head groups turn and contact the shaft…conformational changes that allows ADP —> ATP
Takes 4H+ to completely turn the subunit enough to make 1 ATP
***not substrate-level phosphorylation
Turns 100X per second
If the H+ gradient gets too steep…
ATP synthesis stops
Not enough energy to push more protons against that gradient in the ETC
= respiratory control
= consequence of ETC being linked to oxidative phosphorylation
Oligomycin
ETC inhibitor
Binds to F0 —>
Closes H+ channel —>
Stops ATP synthesis —>
H+ gradient becomes steeper
RESULT: O2 consumption stops
Rotenone
ETC inhibitor
Common in pesticide
Inhibits e-transfer from complex 1 to oxidized ubiquinone
RESULT: everything upstream remains reduced…everything downstream = oxidized
Antimycin A
ETC inhibitor
Blocks CytoC —>
Oxidation of reduced ubiquinol and transfer of e- to complex 3 is stopped
RESULT = NADH, Q, and cytochrome B are reduced …the rest (downstream) stay oxidized
Cyanide and carbon monoxide
ETC inhibitor
Inhibits cytochrome oxidase in complex 4
Preventing final reduction of O2
RESULT: entire chain is reduced except for O2 at the end
Atractyloside
Inhibits ATP/ADP antiporter
Inhibiting oxidative phosphorylation
2, 4 - dinitrophenol (DNP) and FCCP
ETC uncoupler
In acidic cytosol…binds to H+ makes it neutal…so it can re-enter through the IMM
RESULT: disrupts the gradient
Thermogenin
Natural ETC uncoupler
In shoulders and back brown fat
Produces heat for the body
RESULT: dirsupts the H+ gradient
Niclosamide (NEN)
Salt of a drug usually used to treat tapeworms,
Now under investigation for a potential Type II diabetes medication
Effect of pyruvic or lactic acid in cytosol
Lowers cytosolic pH
—> F1 subunit dimerizes —> inhibits ATP synthase reaction
What else uses the gradient as means of transport across the MM?
- Phosphate = symport with H+ ions into matrix
- Pyruvate = symport with H+ into matrix
- ADP/ATP antiporter
Total yield per glucose after ETC…
30-32 ATP
Depending on which shuttle used
