Oxidative Phosphorylation Flashcards
Describe permeability of outer mitochondrial membrane.
Permeable to small molecules and small proteins.
Describe permeability of inner membrane.
Impermeable to small and large molecules
Where does oxidative phosphorylation occur?
Inner mitochondrial membrane
Explain how you can have an electrochemical gradient with no membrane potential.
Negative membrane potential inside, positive membrane potential outside.
What is the fastest way and preferred way for NADH to shuttle H+?
Take it straight to complex I of ETC from cytosol to mitochondrial matrix
What is a slower, irreversible way for NADH to shuttle H+ to ETC?
NADH transfers H+ to glycerol 3-phosphate which then moves into the inner mitochondrial matrix where FAD takes the H+ and moves it to CoQ of the ETC.
Describe the function of the first complex in ETC and its name.
NADH Dehydrogenase complex
Transfer electron from NADH to chain of iron-sulfur clusters. Reduces ubiquinone to ubiquinol. Then Ubiquinone or CoQ transfers protons to next complex.
Describe function of third complex in ETC.
Cytochrome b-c1 complex - CoQ recycling and transfer of electrons to cytochrome C
Describe function of fourth complex in ETC.
Cytochrome oxidase
- 4 electrons enter one at a time from cytochrome c
- Cu, protein side chains, Fe atom on cytochrome oxidase collect all the electrons
- O2 binds to the active site and is reduced
- 4 protons are pumped out of matrix back into intermembrane space
How many H+ ions does it take to make 1 ATP?
About 3
Describe protein transport conformations of cytochrome oxidase.
Conformation A - high affinity for H+, proton uptake
Conformation B - H+ binds to cytochrome oxidase
Conformation C - low affinity for H+, proton released to outside of cell
What is the total aerobic energy yield from one molecule of glucose? Break down where the ATPs come from.
32 ATP total
Glycolysis (2 NADH, 2 ATP)
PDH complex (2 NADH)
TCA (6 NADH, 2 FADH2, 2 GTP)
What is the total anaerobic energy yield from one molecule of glucose?
2 ATP total
What binding-specificity does electron transport rely on for stability and energy efficiency?
Binding-specificity of mobile carriers with complexes I-IV
Where is ubiquinone a free carrier?
Lipids
Where is cytochrome C a free carrier?
intermembrane space
How will a low NAD:NADH ratio affect respiration?
It will slow it b/c there is no reducing agent available
How will a steep proton gradient affect respiration?
It will slow it b/c it will slow electron transfer
How will a high ADP level affect respiration?
It will increase it
What is an NADH dehydrogenase inhibitor of ETC?
Amytal rotenone
What is a cytochrome b-c1 complex inhibitor of ETC?
Antimycin A
What are some cytochrome c oxidase inhibitors of ETC?
CN, CO, azide
What is an F1FoATPase inhibitor?
Oligomycin
What is an ATP/ADP exchange inhibitor?
Atractyloside bongkrektate
What are some uncouplers of respiration? How do they work?
FCCP, DNP (they collapse the H+ gradient)
They collapse the proton gradient and thus allow protons to re-enter the mitochondrial matrix without energy being captured as ATP—the energy is released as heat and the
process is called non-shivering thermogenesis. This prevents the synthesis of ATP but will normally increase respiration and electron transport.
What is a reactive oxygen species and how does it form?
Electron transfer in the mitochondria occasionally allows oxygen to escape before it is fully reduced to water. Escape as a superoxide anion radical (-O2) can lead to the formation of H2O2 or the hydroxyl radical (ROS) which can induce DNA and protein damage.
What do superoxide dismutase and glutathione peroxidase do?
Converts superoxide anion radical into intermediary H2O2 before glutathione peroxidase adds an H, making a water molecule.
How are mitochondrial myopathies obtained?
They are maternally inherited defects in genes encoding mitochondrial tRNAs. Mitochondrial DNA mutates at a much faster rate than nuclear DNA, increasing chance of mitochondrial myopathies.
How do mitochondrial myopathies present?
Muscle weakness and/or neurological symptoms
What are the two categories for mitochondrial myopathies?
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes)
MERRF (myoclonic epilepsy and ragged red fibers)
