T2 L4: Mitochondrial respiratory chain Flashcards

1
Q

Which mitochondrial membrane is impermeable to small molecules and ions?

A

The inner membrane. So it determines what goes in and out

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2
Q

On which mitochondrial membrane is the e- transfer chain located?

A

The inner membrane

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3
Q

What 2 soluble proteins link the reactions between the 4 complexes of the e- transport chain?

A

Ubiquinone (co-enzyme Q/10) and Cytochrome C

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4
Q

Describe the structure of ubiquinone

A

A lipid soluble benzoquinone with a long isoprenoid tail

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5
Q

Which enzyme is linked to complex I of the e- transport chain?

A

NADH dehydrogenase

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6
Q

Which enzyme is linked to complex II of the e- transport chain?

A

Succinate dehydrogenase

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7
Q

Which enzyme is linked to complex III of the e- transport chain?

A

Ubiquinone (cytochrome c oxidoreductase)

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8
Q

Which enzyme is linked to complex IV of the e- transport chain?

A

Cytochrome oxidase

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9
Q

Which complexes does cytochrome c move between?

A

Between complex III and IV

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10
Q

In the e- transport chain, what is the energy from FAD and NAD used to do?

A

Pump H+ into the intramembrane space of mitochondria

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11
Q

Describe what happens in complex I of the e- transfer chain

A
  1. e- are passed to FMN to produce FMNH2
  2. transfer to a series of iron-sulphur clusters which accept e-
  3. Then transfer to ubiquinone
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12
Q

In which complex of the e- transport chain is the overall reaction NADH + H+ + Q = NAD+ + QH2?

A

Complex I

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13
Q

Describe what happens in complex II of the e-transport chain

A
  1. FAD within complex II is reduced to FADH2 by e- gained from the conversion of succinate to fumarate in the TCA cycle
  2. Complex II then passes e- to ubiquinone
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14
Q

What is QH2?

A

Reduced ubiquinone

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15
Q

Describe what happens in complex III of the e- transport chain

A

It’s a proton pump

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16
Q

Describe what happens in complex IV of the e- transport chain

A

It the final proton pump which carries e- from cytochrome C to O2 to produce water e

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17
Q

What is the final e- acceptor in the e- transport chain?

A

O2 to produce water

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18
Q

What is the equation for ATP formation including the charges?

A

ADP3- + Pi2- + H+ = ATP4- + H2O

19
Q

What is Adenine nucleotide translocase and what is its function?

A

An integral protein of the inner mitochondrial membrane that transports ADP3- from the intramitochondrial membrane space into the matrix in exchange for ATP4-

20
Q

Why is the electrochemical gradient favoured by Adenine nucleotide translocase?

A

The H+ has created a very positive intramembrane space so exchange of ADP3- for ATP4- is favoured because of the charges on those molecules. This makes it a passive process

21
Q

What is an antiporter?

A

Something that transports 2 molecules in different directions

22
Q

Name an inhibitor of adenine nucleotide translocase

A

Atractyloside, a glycoside isolated from a thistle

23
Q

What is the function of phosphate translocase?

A

It transports both phosphate and hydrogen ions into the matrix

24
Q

What is a symporter?

A

Something that transports 2 molecules in the same direction

25
Q

Why is the function of phosphate translocase favoured by the electrochemical gradient?

A

H+ travel down the electrochemical gradient and bring the H2PO4- along with it

26
Q

Give an example of a F-type ATPase

A

ATP synthase

27
Q

What are the 2 functional domains of ATP synthase?

A
  1. Fo, an oligomycin-sensitive proton channel embedded in the mitochondrial membrane
  2. F1, an ATP synthase
28
Q

What 3 proteins work together in the mitochondrial membrane to bring in the raw materials into the matrix of mitochondria so ATP can be produced?

A

ATP synthase, phosphate translocase, and Adenine nucleotide translocase

29
Q

Describe the structure of ATP synthase

A

Fo is formed of 3 subunits - a,b, and c

F1 if formed of 5 subunits - 3 alpha, 3 beta, 1 gamma, 1 delta, and 1 epsilon

30
Q

Which subunits of ATP synthase have catalytic sites for ATP synthesis?

A

The 3 beta subunits

31
Q

How are the subunits of ATP synthase arranged?

A

Alpha and Beta subunits alternate on top like an orange. Gamma forms the stalk and epsilon forms the base of the stalk. Delta subunit interacts with the 2 ‘b’ subunits of Fo

32
Q

Describe the theory of rotational catalysis of the ATP synthase

A

A beta subunit starts in conformation for binding ADP and pi and then changes conformation so the active site now binds the ATP tightly. Then the structure changes again to give the active site a lower affinity for ATP so ATP is released

33
Q

What process drives the theory of rotational catalysis?

A

The re-entering of H+ through ATP synthase

34
Q

How much ATP is produced from the oxidation of glucose?

A

30 or 32

35
Q

What effect do uncoupling regents have on the body and how do they work?

A

Normally e- flow and phosphorylation are tightly coupled but uncouplers dissipate the pH gradient by transporting H+ back into the matrix of mitochondria by bypassing the ATP synthase.

36
Q

What is UCP1?

A

Uncoupling protein 1 and thermogenin

37
Q

Where is UCP found and how does it work?

A

It’s found in brown adipose tissue and has specific H+ channels through which [H+] can dissipate. The energy is released as heat instead

38
Q

What is brown adipose tissue (BAT) specialised for?

A

Heat generation

39
Q

What 2 features of brown adipose tissue make is specialised?

A

High numbers of mitochondria which contain UCP1

40
Q

At what age is brown adipose tissue most important?

A

In new-borns because they are susceptible to hypothermia

41
Q

What is DNP and how does it work?

A

An exogenous uncoupler that collects protons from the IMS and moves through the membrane with it, depositing it in the matrix

42
Q

Which uncoupler can be used for weight-loss?

A

DNP

43
Q

How does toxicity from DNP arise?

A

Toxicity through liver damage, reparatory acidosis and hyperthermia