2.2.2. Phosphorylation Flashcards
Oxidative Phosphorylation Poisons: Electron Transport Inhibitors (there are four)
1) Rotenone
2) Cyanide
3) Antimycin A
4) Carbon Monoxide
Oxidative Phosphorylation Poisons: ATP Synthase Inhibitors (there is one)
1) Oligomycin
Explanation: directly inhibits mitochondrial ATP synthase causing an increased proton gradient
Oxidative Phosphorylation Posions: Uncoupling Agents
1) 2,4-dinitrophenol
2) aspiring overdose
3) thermogenin (brown fat)
Explanation: results in increased permeability of the membrane, causing decreased proton gradient and increased O2 consumption. ATP synthesis stops, but electron transport continues; produces heat.
What is the final electron acceptor in the
ETC?
O2
Complex I
NADH dehydrogenase
Complex II
succinate dehydrogenase
Complex III
cytochrome b-c1 complex or CoQ:C1 oxidoreductase
Complex IV
cytochrome oxidase (O2–> H2O)
Complex V
(F0F1 ATPase) ATP Synthase; couples the movement of H+ across the inner mito membrane to ATP synthesis from ADP + Pi
Where does NADH pass its electrons to?
FMN (flavin mononucleotide)
Where does FMN pass electrons to?
through a series of Fe-S centers to Coenzyme Q: accepts e- one at a time forming semiquinone, then ubiquinol (energy produced by e- transfers pumps H+ into cytosolic side of inner mito membrane)
CoQ passes electrons to…
Cytochrome b and c1 through Fe-S centers
Cytochrome c1 passes electrons to
cytochrome c; energy of e- transfers pumps H+ across the membrane
Oxygen is reduced to water by…
electrons transferred from cytochrome aa3, which receives electrons from cytochrome c
Where do the electrons from FADH2 enter the ETC?
Complex II; transfers election to CoQ without associated proton pumping across inner mito membrane
ATP synthase conformations:
Loose
ADP + Pi
ATP synthase conformations:
Tight
ATP
ATP synthase conformations:
Open
release ATP
__ ATP/NADH
2.5 ATP
__ ATP/FADH2
1.5 ATP
Why is cyanide poisonous?
CN blocks oxygen at the aa3 complex, so the ETC has no final electron acceptor
MERRF
myotonic epilepsy & ragged red fibers
- faulty tRNA for leucine
- proliferation and aggregation of mitochondria
- progressive muscle weakness
LHON: Leber Hereditary Optic neuropathy
90% caused by mutation of Complex I subunit
- maternally inherited
- acute optic atrophy with late onset, sudden presentation with blindness (15-35 yoa)
MELAS
mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
- faulty tRNA for lysine
- also ragged red fibers