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64 Cards in this Set

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What is the purpose of the ETC?
To create a chemical and pH gradient across the mito INNER membrane, storing energy.
What do electrons flowing thru the ETC eventually do?
Reduce O2 to water.
What is the work done by electron flow?
Pumping of protons out of mito matrix into innermembrane space.
Why is the mito inner membrane a good place for the ETC? (2 reasons)
1. ATP synthase and ETC carriers are embedded in it.
2. It is impermeable to chrgd molecules - metabolites only cross if they have a carrier.
How do metabolites get into the outer membrane of mitochondria?
It is porous - they diffuse
How does Pi get into the mito matrix?
By symport transport with H+ - set up by PMF set up by ETC.
How does ADP get into the matrix for ATP synthesis?
It is exchanged for ATP by an exchange transporter
What factor will limit the uptake of ADP?
Low ATP - if it's not available for exchange.
What is the charge of the matrix with respect to the intermembrane space?
Negative
What are the 2 shuttles for getting NADH into the matrix?
-Glycerol Phosphate shuttle
-Malate-aspartate shuttle
What happens to NADH at these shuttles?
The electrons are transferred to the matrix, but not NADH itself.
Glycerol phosphate shuttle:
-Rev/irrev?
-Where?
-Yield?
-Irreversible
-Skeletal muscle & brain
-Yields FADH2 inst of NADH
Malate-Aspartate shuttle:
-Rev/irrev?
-Where?
-Yield?
-Irreversible
-Liver and Heart
-NADH
How does the Glycerol-3-P shuttle work?
1. NADH reduces DHAP -> G3P
2. Integral membrane G3P dehydrogenase remakes DHAP; e- go to Ubiquinone in membrane.
Why is the Malate-Asp shuttle better than Glyc3Phosphate?
Malate takes the electrons of NADH directly into the matrix.
How do the electrons get from NADH to malate? Enzyme?
NADH oxidizes Oxaloacetate via Cytosolic Malate Dehydrogenase
How does Malate get into the matrix?
It gets exchanged for a-KG.
What happens to Malate once inside the matrix? Enzyme?
Malate gets reoxidized by Mitochondr Malate Dehydrogenase - remakes Oxaloacetate and NADH
What is necessary for the Mal-Asp shuttle to be complete?
Oxaloacetate converted to Asp which can transport to cytosol.
What allos Asp transpot from the matrix to the cytosol?
It gets exchanged for Glutamate.
How is glutamate useful in the matrix?
It accomplishes 2 things:
-Converts OAA to Asp (vital)
-That converts Glu -> aKG (which exchanges for Malate (step 1)
So what 2 membrane exchanges take place?
1. Malate in for a-KG out
2. Asp out for Glutamate in
What is an important point about Mitochondrial Malate Dehydrogenase?
It is the same enzyme used in the last step of TCA.
What are the major differences between NAD+ and FAD?
-When oxidized, NAD+ is pos charged; FAD is neutral.
-NAD+ only able to gain 2-
-FAD is able to gain 1 OR 2
3 types of electron carriers in the mito inner membrane:
-Ubiquinone (coenzyme Q)
-Iron-sulfur clusters
-Cytochromes
What are the important features of Coenzyme Q?
-A component of Complex I
-Accepts 1 or 2 electrons
What are the important features of Iron Sulfur clusters?
Iron can be ferric or ferrous
Where are Cytochromes found?
In all electron transport complexes
Which cytochrome is especially important?
Cyt-c - carries e- between complexes III and IV.
What's a good way to remember that Ubiquinone is in the inner membrane?
It's very greasy so it likes to live among lipids.
How many electrons can Iron Sulfur clusters carry?
Only one at a time.
How do the various cytochromes differ?
in their side chains.
What is the important component of cytochromes that carries e-?
Heme
What terms describe the simultaneous redox rxns accomplished by ETC?
NADH oxidation: EXERGONIC

ATP production: ENDERGONIC
DeltaG of NADH oxidation:
-52
DeltaG of ATP synthesis:
+7.5
How does the energy of NADH get couple to ATP synthesis?
As e- flow through ETC protons get pumped out and establish a proton gradient.
What is the deltaG of this proton pumping?
Positive - it uses some of the energy in NADH.
What balances the loss of energy by proton pumping?
Electrons flow to progressively more easily reduced carriers.
How many protons get pumped by:
-Complex I
-Complex III
-Complex IV
I = 4
III = 2
IV = 4
How many protons get pumped per
-NADH
-FADH2
10 for NADH
6 for FADH2
Why only 6 protons for FADH2?
It bypasses Complex I and passes its electrons directly to Ubiquinone.
What reaction happens at the end of the ETC?
1/2O@ + 2 H+ -> H2O
But Complex IV waits until there are 4 e- so really 1 O2 -> 2H2O
How do E'v and delta G change as electrons flow through ETC?
E'v gets more pos
DeltaG gets more neg
-Hence reduction of electron carriers gets easier.
How many protons does it take to make an ATP?
4
What is the name of Complex II? What pathway is this in?
Succinate dehydrogenase - in the TCA cycle
What does Succinate dehydrogenase do?
Takes the FADH2 made in converting Succinate to Fumarate, and gives the electrons to the ETC directly!
When are redox reactions thermodynamically favored?
When electron flow is toward species with more positive E.
What is the equation for converting Delta E to G?
G = -nFE
What has a higher absorbance; NADH or NAD+? Cyt CFe2+ or Fe3+?
NADH
Fe2+
So in general what is the effect of oxidation on a molecule's absorbance?
Reduces it.
What happens to e- flow through ETC when [H+] of intermembrane space is high?
It ceases - protons can't get pumped out until ATP synthesis reduces the gradient.
Re: mitochondria, what is
-State 3
-State 4
State 3 = normal working

State 4 = normal resting
What is the rate limiting factor for a normal working mitochondria?
The Respiratory chain - electrons can only flow so fast thru the ETC.
What will the steady-state % reduction of e- carriers in ETC be in
-State 3
-State 4
3: progressively less reduced (53, 20, 16, 6, 4)

4: Still progressively less reduced, but more reduced than for state 3 (99, 40, 35, 14,0)
What is the rate limiting factor for state 4 resting mitochondria?
ADP - Respiration rate is slow b/c ATP is not being burned so ADP levels are low
What will be the effect on e- carriers if oxygen is unavail?
The steady state % of reduction will be 100% for all - they are all fully reduced.
What will be the effect on e- carriers if NADH is unavailable?
All will be fully oxidized - 0% reduced.
What are the symptoms of Complex III defect due to partial deficiency?
Myopathy
-Muscle weakness
-Lactic acidosis
-Decr. phosphocreatine levels
What poisons inhibit complex IV reversibly?
Cyanide CN
Carbon Monoxide CO
What poison inhibits complex IV irreversibly?
Nitric Oxide NO
What else does Nitric Oxide inhibit?
Destroys FeS centers of complexes I and II (at high levels)
What drug inhibits complex III?
Antimycin A
What 2 drugs inhibit Complex I?
Rotenone
Amytal