Oxidative Phosphorylation Flashcards

1
Q

What is the direct generation of ATP by the action of kinases called?

A

Substrate-level phosphorylation.

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2
Q

The bulk of cellular ATP is generated in the mitochondria in a process known as what?

A

Oxidative phosphorylation.

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3
Q

Where does OP take place?

A

The reactions of oxidative phosphorylation take place in the inner membrane, in contrast to the Krebs Cycle reactions which occur in the matrix.

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4
Q

How does the cristae allow for more OP?

A

Numerous folds within the cristae increase the surface area upon which oxidative phosphorylation can take place.

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5
Q

Are the ΔGs of the redox reactions of NADH and FADH2 higher or lower than the ΔG of the hydrolysis of ATP?

A

Higher

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6
Q

What are the four membrane proteins in the electron transport chain?

A

Complex I (a.k.a NADH-Q oxidoreductase or NADH dehydrogenase)

Complex II (a.k.a. Succinate-Q reductase or succinate dehydrogenase)

Complex III (a.k.a. Q-cytochrome C oxidoreductase)

Complex IV (a.k.a. cytochrome c oxidase)

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7
Q

What are the two mobile carriers for the ETC?

A

Co-enzyme Q (a.k.a. ubiquinone)

Cytochrome C

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8
Q

What complexes accept electrons and what does this do?

A

Complexes I, III and IV accept electrons and in doing so, a proton (H+) from the aqueous solution. As electrons pass through each of these complexes, a proton is passed or ‘pumped’ to the intermembrane space.

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9
Q

What does complex II use as a co-factor? What happens to this co-factor?

A

It uses FAD as a cofactor and can communicate directly with Coenzyme Q which is also in the membrane.
As electrons are passed from FADH2 to Coenzyme Q it also picks up a pair of protons, thereby regenerating FAD and forming QH2.

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10
Q

Why does using FADH2 result in less ATP than NADH?

A

Since we have effectively bypassed complex I, fewer protons are pumped to the intermembrane space when FADH2 is reoxidized compared with NADH.
As protons flowing back into the matrix via ATP synthase are used to generate ATP, fewer ATP molecules are generated from the reoxidation of FADH2 compared to NADH.

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11
Q

What is ATP synthase and what is its structure??

A

ATP synthase is a multimeric enzyme consisting of a membrane bound part, F0, and a F1part which projects into the matrix space.

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12
Q

What does the rotation of the enzyme do?

A

Rotation of the enzyme drives transitions states, with altering affinities for ATP and ADP. As a consequence, conformational energy flows from the catalytic subunit into the bound ADP and Pi to promote the formation of ATP (chemical energy).

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13
Q

What does the direction of the rotation of the enzyme dictate?

A

The direction of proton flow dictates ATP Synthesis v ATP Hydrolysis, i.e. depending on the direction of the flow of protons through the ATP synthase, the complex can either generate ATP or consume it.

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14
Q

Where do the protons move if ATP is being made?

A

Net movement of protons flowing into the matrix means ATP is made.

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15
Q

Where do protons move if ATP is being destroyed?

A

Net movement of protons flowing out of the matrix means ATP is consumed.

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16
Q

How much ATP does a sedentary male need in a day?

A

83kg of ATP

17
Q

What is the lifespan of an ATP molecule?

A

1-5 minutes.

18
Q

How much ATP does a person have at one time?

A

250g

19
Q

What is the consequence of our daily ATP demands compared to the amount of ATP we have at one time?

A

Any interruption to the process of oxidative phosphorylation/ATP synthesis, means that a cell rapidly becomes depleted of ATP and is likely to die.

20
Q

What is the most common cause of OP failure?

A

The most common cause of a failure of oxidative phosphorylation is simply a lack of oxygen e.g. hypoxia (diminished), anoxia (total).

21
Q

How long does it take for cell death once OP has stopped?

A

Depending on the cell type and their metabolic requirements, death will be within a few minutes (neurons) or a few hours (muscle).

22
Q

What is the uptake of oxygen by mitochondria controlled by?

A

Uptake of oxygen by mitochondria is controlled by the components of ATP production:Inorganic phosphate (Pi), and ADP.
This is known as respiratory control and allows the body to adapt oxygen consumption to actual energy requirements.

23
Q

What doe metabolic poisons do?

A

They interfere with either the flow of electrons along the ETC or the flow of protons through ATP synthase, interrupting ATP synthesis.

24
Q

How does cyanide work?

A

It binds with high affinity to the ferric (Fe3+) form of the haem group in the cytochrome oxidase complex blocking the final step of the ETC.

25
Q

How does azide work?

A

It binds with high affinity to the ferric (Fe3+) form of the haem group in the cytochrome oxidase complex blocking the final step of the ETC.

26
Q

How does malonate work?

A

M​alonate closely resembles succinate and acts as a competitive inhibitor of succinate dehydrogenase. It slows down the flow of electrons from succinate to ubiquinone by inhibiting the oxidation of succinate to fumarate.

27
Q

How does rotenone work?

A

It inhibits the transfer of electrons from complex I toubiquinone.

28
Q

How does oligomycin work?

A

Oligomycin is an antibiotic produced by Streptomyces that inhibits oxidative phosphorylation by binding to the ‘stalk’ of ATP synthase and blocking the flow of protons through the enzyme.

29
Q

How does dinitrophenol (DNP) work?

A

Dinitrophenol (DNP) is a proton ionophore that can shuttleprotons across the inner mitochondrial membranes.

30
Q

What did we use to use DNP for and why?

A

Dinitrophenol can induce weight loss by transporting protons across the mitochondrial membrane, thereby uncoupling oxidative phosphorylation from ATP production and markedly increasing the metabolic rate and body temperature.

31
Q

Why did we stop using DNP?

A

The margin between the slimming dose and that required to poison or kill is slight - so slight that several patients died and many suffered permanent injury before use of the drug was abandoned in 1937.