Uncoupling and Oxidative Phosphorylation Flashcards

1
Q

What does coupling mean for the measurement of energy expenditure?

A

We can measure the rate of fuel oxidation to tell us the rate of energy expenditure through rate of oxygen consumption or carbon dioxide production.

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2
Q

How can uncoupling occur? What does this cause?

A

If there is a leak/hole in the membrane allowing H+ to come through without the ATP synthase. This destroys the gradient and so protons will be pumped out very fast and with a lot of pressure - no ATP synthesis.

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3
Q

What are the effects of having no proton gradient?

A

There is no driving force for ATP, instant regeneration of NAD and NADH and no ATP synthesis.

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4
Q

What happens when there is no driving force for ATP due to uncoupling?

A

No back pressure to stop H+ pumping and no restriction of H/e movement down the transport chain to oxygen.

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5
Q

What happens when there is instant regeneration of NAD and FADH due to uncoupling?

A

Massive fuel oxidation rate and huge oxygen consumption.

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6
Q

What happens when there is no ATP synthesis due to uncoupling?

A

ATP levels and cell death.

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7
Q

What are the features of DNP?

A

Hydrophobic when protonates and can move across the membrane. Weak acid and when H comes off the negative charge can be delocalised. Also hydrophobic when charge changes.

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8
Q

What is the mechanism of DNP? What does this lead to?

A

Dissipation of proton gradient. Massice weight loss and what production - sometimes used as weight loss agent (uses lots of ATP and cells can die).

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9
Q

What is UCP-1? What does it do?

A

Uncoupling protein 1 is a natural uncoupler. Thermogenin. Acts as a channel allowing protons to move from the cytosolic side to the matrix (bypass ATP synthase).

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10
Q

Where is UCP-1 found?

A

In brown adipose tissue.

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11
Q

What is the function of thermogenin?

A

Function is to generate heat. Important in babies, small mammals and hibernating animals.

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12
Q

What is thermogenin controlled by?

A

Hormones. Noradrenaline binds to the beta 3 receptor on the cell surface to stimulate fatty acid release. This opens the proton channel.

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13
Q

How are we able to identify BAT in adults? Where is it located?

A

Contain UCP-1 and B3 receptors. In shoulder blades and around kidneys.

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14
Q

How many complexes are in the electron transport chain?

A

4 complexes embedded in the mitochondrial membrane.

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15
Q

Each complex in the electron transport chain contains many ______. There are two groups of these _____ and ______.

A

Proteins. Structural (maintain the shape of the complex) and Prosthetic (transport H/e).

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16
Q

The proteins are arranged in what way for the complexes in the ETC?

A

H+ expelling reactions on the outside and H+ consuming reactions on the matrix side.

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17
Q

Approximately ____ are pumped out for each NADH coming into the matrix of the complex in the ETC.

18
Q

In the ETC what happens to NADH?

A

Complex 1 takes H from NADH and reoxidises it to NAD. NAD rips H/e off -CH-OH groups, converting them to -C=O groups.

19
Q

Which part of NAD accepts electrons and protons and what is it derived from?

A

Nicotinamide group derived from nicotinic acid. Accepts 2 electrons and a proton.

20
Q

Which part of FAD accepts 2 hydrogens (2 protons and two electrons)?

A

Adenine residue at base coupled to ring structure called FMN.

21
Q

What happens in complex 2 of ETC?

A

FAD gets stuck in complex 2 - accepts and donates H’s and rips H from a saturated hydrocarbon chain.

22
Q

What is UQ?

A

Ubiquinone - lives inside mitochondrial membrane - picks up H’s from Complex II,
is reduced to UQH2 which transfers H’s to complex III.

23
Q

What happens to electrons in complex 1?

A

Move from one prosthetic group to another until they reach the Q pool.

24
Q

What is the Role of Cytochrome C in the ETC?

A

Picks up e- from complex III and gives the e- to complex IV. Also has a prosthetic group that constrains an iron atom.

25
What happens to the iron atom contained in the prosthetic group of Cyt C?
Changes from ferrous to ferric as it loses electrons and other way around as it gains them.
26
How are iron atoms held in place?
By a scaffolding (heme rind or part of the iron sulphur cluster.
27
What is the mechanism for proton pumping in the electron transport chain?
Orientation of the uptake/release of H+ allows for net translocation of H+. Proton releasing reactions on cytoplasm side Proton consuming reactions on the matrix side. (Card 8).
28
What happens is the local (just around pumping area) pH is higher than in the matrix?
Lead to an increase in proton gradient in these areas.
29
What are the two components of the force of the proton gradient?
Charge and concentration. | The difference in pH gives it potential difference and also in concentration of protons drives it as well.
30
How do we get cytoplasmic NADH to the ETC?
From NADH generated in glycolysis. (Card 9)
31
What are the four routes to Q?
``` Complex I Complex II From the first step of beta-oxidation From glycerol 3-P shuttle (Card 10) ```
32
What is another way of uncoupling that involves Q in the ETC?
Sending hydrogens from NADH directly to oxygen - igniting hydrogens - uses alternative dehydrogenase and sends directly to Q.
33
How are free radicals formed?
Electrons in the UQ pool can react with molecular oxygen.
34
What can free radicals cause?
Mutations to DNA - can also collide into proteins and damage them.
35
How can the body get rid of free radicals? When are free radicals less likely to form?
Use group of compounds with reduced thiol groups - mop up oxygen free radicals. Less likely if complex III is vacant.
36
The ATP synthase uses movement of ___ protons to make ____ ATP.
3. 1.
37
What is the significance of the F0F1ATPase structure?
Beta subunit of F1 to change in conformation in 3 ways: to accept ADP and Pi, reacting them together to give ATP and releasing ATP.
38
How does the F0F1ATPase work?
Card 11.
39
What causes the B subunit to change conformation?
Every time three protons come in.
40
What are the inhibitors and acceptors of the ETC?
Card 12