MCB Lecture 14, Oxidative Phosphorylation Flashcards

0
Q

Describe the overall process of the electron transport chain

A
  1. NADH docks at Complex I and is converted to NAD+, releasing 2e-
    The electrons move through Complex 1 on the FMN and Fe-S clusters
    Electrons reduce Ubiquinone to Ubiquinol
    Q -> QH2
  2. Ubiquinol diffuses through the membrane (lipophilic) to Complex III.
    4 H+ protons are pumped from the matrix to the intermembrane space per NADH at complex I
  3. Coenzyme Q : Ubiquinone. Is reduced by electrons from NADH at CI and electrons from FADH2 from CII
  4. Complex II is also known as succinate dehydrogenase.
    Here, succinate docks and is turned into fumarate, generating FADH2.
    Electrons from FADH2 -> Fe-S -> Q -> QH2.
  5. Complex III has a cavern with a ubiquinol docking site. The electrons end up on cytochrome C.
    4 protons are pumped (per 1 NADH)
  6. Cytochrome C shuttles electrons from CIII to CIV.
    the Fe3+ centre of the heme C prosthetic group accepts the electrons
  7. Complex IV has a docking station for cytochrome C.
    The electrons from cyt. c move through various groups are accepted by O2.
    2 H+ are pumped into IMS and four H+ are used in the reduction of O2 -> H2O
  8. This sets up a Chemiosmotic gradient: there are many protons in the intermembrane space that want to diffuse back.
    At ATP synthase, protons diffuse through the F0 subunit, causing the gamma- subunit of F1 to rotate.
    This allows the normally unfavourable reaction ADP + Pi -> ATP to happen
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1
Q

What are all the compounds we have got from Glycolysis, PDH complex, TCA cycle?

A

Glycolysis: net 2 ATP, 2 NADH
PDH: 2 NADH
TCA cycle: 6 NADH, 2 FADH2, 2 GTP

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2
Q

Describe the structure of Complex I

A

Large L shaped protein with 42 subunits

A FMN-containing flavoprotein
6 Fe-S clusters
A N-2 iron sulfur protein

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3
Q

Describe the structure of Complex II

A

4 protein subunits: A, B, C, D

A and B are in the matrix
C and D are transmembrane

Contains two types of prosthetic groups:
A-B: Fe-S clusters, FAD, Succinate binding site
C-D: heme group: heme b and Q binding site

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4
Q

Describe the structure of Complex III

A

Three subunits:
1. Cytochrome B
Two cyt B subunits form a cavern

Caven: Qn and Qp binding sites
Coenzyme Q moves from matrix (Qn) to IMS (Qp)

  1. Rieske Iron-Sulfur proteins
  2. Cytochrome C
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5
Q

Describe the structure of Complex IV

A

4 core subunits
Subunit I
Two heme groups (a and ac)
Copper ion (Cub)

Subunit II
2 copper ions Cua
Cyt c binding site

Subunit III
Essential for H+ movement

Subunit IV
Unknown role, but pumps 2H+

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6
Q

Describe the characteristics of Coenzyme Q

A

Lipophilic molecule

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7
Q

What are the two forms of coenzyme Q, and what are their names?

A

Ubiquinone: Q, oxidised

Ubiquinol: QH2, reduced

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8
Q

Describe the structure of Cytochrome C

A
Protein
Prosthetic group (heme c) with iron centre
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9
Q

What is the function of coenzyme Q?

A

Shuttles electrons from Complex I and Complex II to Complex III, where the electrons are transferred to cytochrome c

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10
Q

What is the function of cytochrome C?

A

Transfers electrons between complex III and IV

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11
Q

Which complexes pump protons into the intermembrane space?

A

Complex I, complex III and complex IV

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12
Q

Which complex also has a role in the TCA cycle?

A

Complex II is also known as succinate dehydrogenase

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13
Q

Describe the structure of ATP Synthase

A

F0 stalk and F1 head

F0:
A, B2, C10

F1:
alpha3, beta 3, gamma, delta, epsilon

The head has 3 alpha-beta dimers is a ring. These have different adenine binding sites.

i. Beta-empty
ii. Beta-ADP
iii. Beta-ATP

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14
Q

Describe how rotational catalysis works

A

When protons move through the stalk, the gamma subunit of F1 rotates.

This rotation makes the normally unfavourable reaction ADP + Pi -> ATP occur.

The formed ATP molecules is then released

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15
Q

Describe the three different adenine binding sites in ATP synthase

A

i. Beta empty, this is where ATP has just been release and ADP and Pi will bind when rotated
ii. Beta-ADP, this is where ADP and Pi bind
iii. When the shaft rotates, the molecules become fused together and ATP is bound in this B-ATP site

16
Q

How many protons does it take to synthesise one ATP molecule?

A

About 4

17
Q

How many protons are pumped across the membrane per NADH?

A

2.5

18
Q

How many ATP molecules per FADH2 molecule?

A

1.5

19
Q

How many ATP are generated from one molecule of glucose?

A

30-32

20
Q

Which disease arises from complications with the electron transport chain?
What is the name of the disease?
How does it occur?
What is the mode of inheritance?

A

Paraganglioma.
This involves an autosomal dominant inherited mutation in Complex II, Sunncinate dehydrogenase.

The electrons pass directly from succinate to O2, and reactive oxygen species form such as hydrogen peroxide and superoxide.

These reactive oxygen species cause tissue damage leading to tumours

21
Q

How is paraganglioma treated?

A

Early detection and surgery can treat this diesease

22
Q

What does a faulty Complex II lead to ?

A

Paraganglioma due to electrons passing directly from succinate to O2

23
Q

What are the symptoms of hereditary paraganglioma?

A

Tumours in head and neck.

Especially in the carotid body which is associated with detecting O2 levels in the blood.