Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medical Physiology > Mitochondrial function, inhibition and disease > Flashcards

Mitochondrial function, inhibition and disease Flashcards

You may prefer our related Brainscape-certified flashcards:
USMLE® Step 1 flashcards
1
Q

What is complex 1?

A

The first enzyme in ETC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does complex 1 act?

A

As the rate limiting step for ATP synthesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is complex 1 called?

A

NADH-coenzyme Q oxo reductase.

Or NADH dehydrogenase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the characteristics of complex 1?

A

It is the least well understood of all ETC complexes.

It is the most difficult to obtain a crystal structure for it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How many subunits make complex 1??

A

46 different subunits.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What much molecular mass of 1 giga Dalton does complex 1 have?

A

A huge molecular mass.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where is the complex encoded?

A

Some in the mitochondrial genome.

The rest by nuclear genome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which part of the complex 1 is encoded in the inner mitochondrial membrane?

A

The hydrophobic part.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What part of complex 1 stays out into the lumen of the mitochondria and it is encoded by nuclear genome?

A

The hydrophilic part.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How many subunits out of 46 are important in complex 1 for its catalytic and redox activity?

A

14 of 46 subunits.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do the rest of 46 subunits of complex 1 that are not important for its redox and catalytic activity do?

A

They modulate its activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the function of enzyme complex 1?

A

It catalyses NADH oxidation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

From where does NADH oxidation comes from?

A

From Krebs cycle reactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Where do Krebs cycle reactions for NADH oxidation occur?

A

In the mitochondrial lumen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

By what factor do Krebs cycle reactions for NADH oxidation occur?

A

By ubiquinone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is ubiquinone?

A

A lipid.

Soluble.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Where does ubiquinone sits?

A

In the inner membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does NADH oxidation do?

A

It takes 2 electrons/NADH –> pumps 4 protons –> redox energy released.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does redox energy released from NADH oxidation allow?

A

The pumping of protons from the lumen of the mitochondria across the inner membrane against their concentration gradient.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How many modules does complex 1 have?

A

3 modules.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the three modules of complex 1?

A
  1. Electron input module / dehydrogenase module (N module).
  2. Electron output module / hydrogenase module (Q module).
  3. Proton translocation module (P module).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the function of N module of complex 1?

A

Accepts electrons from NADH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the function of Q module of complex 1?

A

Delivers electrons to ubiquinone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the function of P module of complex 1?

A

Pumps protons across inner membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Which two of the three modules of complex 1 are parts of the matrix arm of the complex?

A

N and Q modules.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Where does the P module of complex 1 lie?

A

Within the portion in the membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What molecule binds to complex 1 firstly?

A

NADH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What does NADH do once it binds to complex 1?

A

It transfers 2 electrons to the flavin mononucleotide / FMN prosthetic group of complex 1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What does the transform of 2 electrons from NADH to the complex 1 do?

A

It recycles NAD+ –> produces H+ –> creates FMNH2 in the complex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Where are the electrons from NADH transferred then?

A

They are transferred through FMN via series of iron-sulphur (Fe-S) clusters –> travel up hydrophilic arm of complex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does the redox state of the protein induces?

A

A conformational change –> alters dissociation constant of side chains –> causes 4 H+ –> pumped from mitochondrial matrix –> across intermembrane space.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What happens to the electrons released from redox reaction in complex 1?

A

They are handed to ubiquinone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How is ubiquinone called alternatively?

A

Co-enzyme Q.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Why is ubiquinone called alternative Co-enzyme Q?

A

Because it is indicated by a Q in the hydrophobic part of the enzyme.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How many electrons from redox reaction in complex 1 does ubiquinone accept?

A

2 electrons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

To what is ubiquinone reduced after it accepts 2 electrons from NADH in redox reaction in complex 1?

A

It is reduced to ubiquinol (CoQH2).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What happens to H+ released from NADH oxidation in complex 1 in the begining?

A

They are trapped in the intermembrane space until they can move back.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Through what can the H+ released from NADH oxidation in the beginning of complex 1 move back?

A

Through UCP1 –> leak across naturally slowly.

Or through ATP synthase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What does complex 1 produce in respiration?

A

Free radicals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are the free radicals?

A

They are highly reactive compounds.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Why are the free radicals highly reactive compounds?

A

Because they have unpaired electrons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

How are free radicals useful?

A

In small quantities –> useful cell signals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What can a build up of free radicals cause?

A

Cell dysfunction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Why a build up of free radicals causes cell dysfunction?

A

Because they damage macromolecules with double bonds.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Where does the damage of macromolecules with double bonds leads to?

A

To inflammation.
Calcium influx.
Cell death if uncontrolled.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What happens if oxygen delivery is blocked?

A

The final electron acceptor is in short supply –> ROS levels build up quickly –> damage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What can produce ROS?

A

Complex 1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Why does complex 1 produces ROS?

A

Because electrons ‘leak’ out –> interact with oxygen –> later complexes work slower.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Where does the production of ROS by complex 1 is important?

A

In cell signalling.
In apoptosis.
Programmed cell death.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

How many complex 1 inhibitors exist?

A

60.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

As what are some of the 60 complex 1 inhibitors developed?

A

As agents used in research.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Why do they use some of complex 1 inhibitors in research?

A

To explore mitochondrial function.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Where else can some other complex 1 inhibitors used?

A

In medicine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What is the most common use of complex 1 inhibitors?

A

As pesticides.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

In how many pesticides group do complex 1 inhibitors fall into and based on what criteria?

A

3 groups.

Based on how they work.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What are the 3 groups that complex 1 inhibitors fall into as pesticides?

A
  1. Quinone antagonists = acetogenins.
  2. Semiquinone antagonists = rotenone.
  3. Quinol antagonists = myxothiazol.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the function of Quinone antagonists as complex 1 inhibitors?

A

They act at the entry of the hydrophobic site.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is the function of Semiquinone antagonists as complex 1 inhibitors?

A

They act in the intermediate steps by disrupting the electron transfer between terminal FeS cluster and ubiquinone.
Unknown specific action site.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is the function of Quinol antagonists as complex 1 inhibitors?

A

They prevent formation and release of product.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Are the inhibitors that prevent NADH interaction with the enzyme of complex 1 specific?

A

No.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Where do the inhibitors of complex 1 act on to prevent NADH interaction with the enzyme?

A

They act on all other enzymes that rely on NADH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Which of the 3 complex 1 inhibitors is the most commonly used?

A

Rotenone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What are Piericidin and Myxobacterial antibiotics?

A

Acetogenins.
Useful anticancer drugs.
Act on complex 1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Where do Tranquiliser barbiturate amytal, some neuroleptic drugs and neurotoxins, capsaicin from hot chilli peppers act?

A

On complex 1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What does the antidiabetic drug Metformin inhibit?

A

Complex 1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Where is the function of the antidiabetic drug Metformin that inhibits complex 1 important?

A

For its function.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Which is the strongest inhibitor of complex 1?

A

Bullatacin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Which organisms are sensitive to complex 1 inhibition?

A

Insects.

Fish.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Why do Rotenone and similar compounds used as pesticides?

A

Because insects and fish mitochondria are sensitive to complex 1 inhibition.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What happens to NADH if complex 1 is inhibited?

A

NADH is not oxidised.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What happens when NADH is not oxidised?

A

There is no supply of NAD+.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What happens when NAD+ supply does not occur?

A

Krebs cycle activity is reduced –> Oxygen consumption slows.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What happens when Krebs cycle activity is reduced?

A

H+ pumping slows down.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What happens when H+ pumping slows down?

A

Membrane gradient is reduced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What happens when the membrane gradient is reduced?

A

protonmotive force is weaker –> the ATP production is slowed down.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What effects can ATP reduction have?

A

Global effects on cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Why does the ATP reduction have global effects on cell?

A

Because all enzymes are affected.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What is the most notable effect caused by ATP reduction?

A

Reduced ion pumping –> K+ leaves cells –> Ca2+ floods in.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

When is the complex 1 inactivated?

A

During ischaemia reperfusion.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What happens during ischaemia reperfusion?

A

Stroke.
Or heart attacks.
–> Tissue damage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What happens to complex 1 in absence of oxygen?

A

It loses FMN co factor.

Becomes inactive.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

In what disease is complex 1 dysfunction implicated?

A

In Parkinson’s disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What do complex 1 inhibitors cause?

A

Cell death.
Changes.
Parkinson’s disease in neurones in cell culture.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

What diseases are associated with complex 1 dysfunction?

A

Several neurological diseases.
Type 2 diabetes.
Cardiac disease.
Various cancers.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Where do neurons and pancreatic isle beta cells rely heavily on?

A

On mitochondrial ATP.

NAD -linked pathways.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What does the reliance of neurons and pancreatic islet beta cells on mitochondrial ATP and NAD-linked pathways makes them?

A

Very vulnerable.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What is the characteristic of cancer cells in culture?

A

They have low mitochondrial density.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

What does the low mitochondrial density of cancer cells in culture make them?

A

More vulnerable to complex 1 inhibition than other cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What are the motor skill symptoms of Parkinson’s disease?

A 
Bradykinesia.
Vocal symptoms.
Rigidity and postural inability.
Tremors.
Walking or gait difficulties.
Dystonia.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What are the nonmotor skill symptoms in Parkinson’s disease?

A 
Mental/behavioural issues.
Sense of smell.
Sweating and melanoma.
Gastrointestinal issues.
Pain.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

How is complex 2 called?

A

Succinate reductase.

Succinate ubiquinone oxidoreductase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

What does complex 2 contain?

A

Succinate dehydrogenase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

What is succinate dehydrogenase?

A

An enzyme in Krebs cycle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

How many protein subunits occur in complex 2 ?

A

4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Which are the 4 subunits in complex 2?

A
  1. Succinate dehydrogenase (SDHA).
  2. Succinate dehydrogenase iron-sulphur subunit (SDHB).
  3. Succinate dehydrogenase complex subunit C (SDHC).
  4. Succinate dehydrogenase complex subunit S (SDHD).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

What do SDHA + SDHB subunits of complex 2 do?

A

They project into the lumen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

What are the subunits C +D of complex 2?

A

They are membrane bound.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

By what genes is complex 2 encoded?

A

By only nuclear genes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

What does succinate dehydrogenase catalyse?

A

Succinate oxidation to –> fumarate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Where does oxidation of succinate to fumarate occur?

A

In the lumen of mitochondria.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

By what subunit of complex 2 does the succinate oxidation to fumarate performed?

A

By SDHA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

What does subunit SDHA of complex 2 in the process of oxidation of succinate to fumarate?

A

It reduces FADH –> FADH2.

Transfers electrons through SDHB via iron sulphur complexes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

How is the process of SDHA transferring electrons through SDHB via iron sulphur complexes called?

A

Electron tunnelling.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Why does SDHA transfers electrons through SDHB via iron sulphur complexes?

A

To oxidise ubiquinone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

Where does ubiquinone oxidation occur?

A

In the inner mitochondrial membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

What happens in ubiquinone oxidation process?

A

Q –> QH2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

By which subunits of complex 2 does Q converted into QH2 in the oxidation process of ubiquinone?

A

By SDHC + SDHC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

What do SDHD + C complex 2 subunits contain?

A

A haem group.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

As what does the haem group of complex 2 SDHD + C subunits act?

A

As electron sink.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

What is the haem group of complex 1 SDHD + C subunits?

A

A protection mechanism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

What is the function of haem group in complex 2 SDHD + C subunits?

A

Stops excess electrons that react with molecular oxygen and form free radicals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Which is the only membrane bound enzyme in Krebs cycle?

A

Succinate dehydrogenase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

Where are the other Krebs cycle enzymes found?

A

In the mitochondrial lumen.

Not membrane bound.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

What does the unique structure of complex 2 mean?

A

It can act as a regulator of metabolism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

Why does complex 2 can act as a regulator of metabolism?

A

Because it is involved in Krebs cycle and ETC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

When does the activity of succinate dehydrogenase drops very low?

A

Below a membrane potential of -60mV to -80mV.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

What happens to the activity of succinate dehydrogenase above -80mV?

A

It has a very high activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

What can the high activity of succinate dehydrogenase control?

A

Krebs cycle during hypoxia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

What happens to ubiquinone during hypoxia in Krebs cycle?

A

It is reduced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

How is the complex 2 characterised in ETC?

A

Unique.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

Why is complex 2 unique in ETC?

A

Because it does not pump protons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

What does complex 2 do in association with complex 1?

A

It runs in parallel to complex 1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

Why complex 2 cannot contribute to protonmotive force?

A

Because it does not pump protons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

What does complex 2 have?

A

A prosthetic group.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

What is the prosthetic group of complex 2?

A

Subunit E.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

What does subunit E in complex 2 do?

A

It helps FAD bind to subunit A.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

How many complex 2 inhibitors exist?

A

2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

Which are the complex 2 inhibitors?

A
  1. Malonate + Krebs cycle intermediates.

2. Carboxin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

What does Malonate and Krebs cycle intermediates do as inhibitors of complex 2?

A

They prevent succinate binding.
Prevent electron build up.
Prevent formation of superoxide radical.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

What does Carboxin do as an inhibitor of complex 2?

A

It prevents ubiquinone binding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

As what are ubiquinone binding inhibitors often used?

A

As fungicides.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

What do some fungi have to fungicides?

A

Developed resistance.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

What happens when complex 2 is inhibited?

A

Proton motive force is not affected.
Free radical production increases.
Low oxygen sensing pathways are switched on.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

What does complex 2 generate when complexes 1 and 3 are inhibited?

A

Large ROS amount.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

What does complex 2 normally generate?

A

Protection against ROS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

What is the importance of complex 2?

A

In making sure quinone pool in the inner membrane is reduced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

As what does complex 2 act?

A

As an antioxidant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

Why does complex 2 act as an antioxidant?

A

Because free radicals steal its electrons –> protect macromolecules from damage by ROS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

What can ROS do and cause damage if complex 2 does not act as an antioxidant?

A

Steal electrons from lipid and nucleic acids.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

What are the consequences of complex 2 inactivation?

A

ROS increases.
DNA mutations increase.
Cell cycle progression increases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

Why does cell cycle progression increases when complex 2 is inactivated?

A

Because p53 protein levels drop.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

What does the increase in succinate signals causes to the cell?

A

Low Oxygen levels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

What is the consequence of low oxygen levels in cell?

A

Hypoxia factor is made.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

What do Hypoxia and complex 2 inactivation cause?

A

Tumours to arise and survive.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

What are the diseases associated with complex 2 characterised?

A

Rare.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

Why are the diseases associated with complex 2 rare?

A

Because complex 2 enzyme is vital.

Any disorders are usually lethal at embryo stage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

Are there any complex 2 disorders?

A

Yes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

What do the complex 2 disorders produce?

A

A wide range of symptoms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

What is one of the complex 2 disorders?

A

Leigh disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

What is the complex 2 Leigh disease?

A

A degenerative neurometabolic disorder.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

What does Leigh disease of complex 2 involves?

A 
Loss of previously acquired motor skills.
Loss of appetite.
Vomiting.
Irritability.
Seizures.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

When do the symptoms of Leigh disease of complex 2 onset?

A

In infants.
3 months old.
2 years old.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

When can Leigh disease of complex 2 begin?

A

Much later in life.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

What are the factors that cause Leigh disease of complex 2?

A

Arginine changes to –> tryptophan.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

Where does arginine change to tryptophan and causes Leigh disease of complex 2?

A

At position 544 in SDHA subunit.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

What does the change of arginine to tryptophan at 544 position in SDHA produces and then causes Leigh disease of complex 2?

A

It slows SDH activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

Where do mutations of iron-sulphur complexes / cytochrome b subunits involved?

A

In electron transfer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

What do mutations of iron-sulphur complexes / cytochrome b subunits in electron transfer cause?

A

Familial neural crest-derived tumours in head / neck.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

Where are neural crest-derived tumours in neck and head from mutations in complexes/ cytochrome b subunits in electron transfer found?

A

In highly vascular organs = carotid body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

What does make the highly vascular organs more reliant on glycolysis for ATP production?

A

The lack of efficiency of ETC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

Where else do SDHD mutations implicated?

A

In the development of Huntington’s disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

What is Huntington’s disease?

A

A hereditary neurodegenerative disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

How is complex 2 important in cancer biology?

A

As a tumour suppressant.

In oxygen sensing.

164
Q

Where else is complex 2 dysfunction involved?

A

In development of diabetes through ROS and succinate production - insulin secretion pancreas link.

165
Q

What are the early symptoms of Huntington’s disease?

A 
Moodiness.
Fidgeting.
Cognitive issues.
Personality shifts.
Depression.
Trouble focusing.
Muscle twitching.
166
Q

What happens during ischaemia?

A

Succinate accumulates due to reversal of succinate dehydrogenase (SDH) activity.

167
Q

As what does accumulated succinate act?

A

As a store of electrons that drive reverse electron transport (RET) + reactive oxygen species (ROS) production.

168
Q

When does accumulated succinate act act as a store of electrons?

A

When it is rapidly re-oxidised on perfusion.

169
Q

When do SDH reversal and succinate accumulation inhibited?

A

During ischaemia.

170
Q

By which substance do SDH reversal and succinate accumulation inhibited during ischaemia?

A

By malonate.

171
Q

What is malonate?

A

A competitive inhibitor of SDH.

172
Q

What happens on reperfusion?

A

Accumulated succinate –> rapidly re-oxidised.

173
Q

By which factor is accumulated succinate re-oxidised on perfusion?

A

By SDH.

174
Q

Where does re-oxidation of accumulate succinate by SDH result?

A

To reverse electron transport (RET).

Superoxide (O2) production from flavin mononucleotide site of complex 1 (C1).

175
Q

What else does competitive inhibitor of SDH = malonate, inhibits?

A

Rapid re-oxidation of succinate by SDH on perfusion.

176
Q

What is the function of malonate in the inhibition of succinate by SDH on perfusion?

A

It prevents RET.

Prevents ROS production.

177
Q

What can be used to treat or reduce ischaemia reperfusion injury?

A

Malonate esters.

178
Q

Wat are the causes of ischaemia?

A

Stroke.

Heart attack.

179
Q

When do stroke and heart attack occur during ischaemia?

A

During ischaemia reperfusion injury.
Surgery.
Transplantation.
Hypovolemic shock.

180
Q

Which tissues are the most vulnerable to ischaemia cuses?

A

Tissues with lots of mitochondria = brain, heart, kidney.

181
Q

As what is complex 3 known?

A

As cytochrome C oxidoreductase.
Co enzyme Q cytochrome c oxidoreductase.
Cytochrome bc1 complex.

182
Q

By how many subunits is complex 3 made?

A

11 subunits.

183
Q

What are the 3 subunits of the total 11 subunits in complex 3?

A

They are respiratory subunits.

184
Q

Where are the 3 respiratory subunits of complex 3 involved?

A

In redox.

In proton pumping.

185
Q

How many proteins occur in the process of redox and proton pumping of the 3 subunits of complex 3?

A

2 core proteins.

6 small accessory proteins.

186
Q

By what are the proteins involved in the 3 subunits of complex 3 encoded?

A

By mitochondrial and nuclear genes.

187
Q

What else does complex 3 have?

A

4 co factors.

188
Q

For what are the 4 co factors of complex 3 required?

A

For the activity of complex 3.

189
Q

Which are the 4 co factors of complex 3?

A
  1. Cytochrome c1.
  2. Cytochrome b 562.
  3. Cytochrome b 566.
  4. Iron sulphur complex.
190
Q

With what does the complex 3 couple?

A

With the inner mitochondrial membrane.

191
Q

What does the reaction of complex 3 called?

A

Ubiquinone .

Q cycle.

192
Q

What does the reaction of complex 3 involve?

A

The reduction of cytochrome c.
Oxidation of cytochrome c.
Oxidation of coenzyme Q.

193
Q

What happens in the ubiquinone reaction of complex 3?

A

4H+ –> pumped in –> inner membrane space.

194
Q

How many protons are taken up from the matrix in the reaction of complex 3?

A

Only 2 H+.

195
Q

What does the fact that : matrix only takes up 2 H+ in the reaction of complex 3?

A

The inter membrane space –> becomes –> more positive relative to matrix.

196
Q

What happens to the 2 electrons after they are taken up by the matrix in the reaction of complex 3?

A

They are transferred from ubiquinol –> to ubiquinone.

197
Q

How are the 2 electrons transferred from ubiquinol to ubiquinone in the reaction of complex 3 after they are taken up by matrix?

A

By the two cytochrome c co factors.

198
Q

How do the cytochrome c co factors help the 2 electrons to transferred from ubiquinol to ubiquinone?

A

Cytochrome b –> binds –> ubiquinone (QH2) in membrane + ubiquinol (Q).

199
Q

Where are cytochrome b and ubiquinone + ubiquinol bind?

A

Within complex 3.

At Qo and Qi sites.

200
Q

What do iron sulphur complex and bL haem group do?

A

They pull 2 electros from the Qo site.
They hand one electron to –> cytochrome c1.
They hand the other electron to –> the other haem group (bH).

201
Q

What does cytochrome c1 in complex 3 do?

A

It hands electrons to –> cytochrome c.

202
Q

What does the other electron in complex 3 do?

A

It tracks down through complex 3.

It hands electron to –> ubiquinone at Qi.

203
Q

How many does the process of electron that tracks down from complex 3 and hands it to ubiquinone Qi occur?

A

Twice.

204
Q

What happens in the process where the electron tracks down from complex 3 and hands it to ubiquinone Qi?

A

It pulls 4 H+ to –> inner membrane space from ubiquinone oxidation.
It removes 2 H+ from matrix –> use in reducing ubiquinol.

205
Q

What is the key think that happens in complex 3?

A

Complex 3 –> pumps H+ as it hands on electrons.
Proton movement = unequal.
Intermembrane space becomes more positive than matrix.

206
Q

Where does the more positive inter membrane space than matrix help?

A

To create and maintain proton motive force for ATP synthesis.

207
Q

Which is one of the main inhibitors of complex 3 used in laboratory settings?

A

A compound called: Antimycin A.

208
Q

What is Antimycin A?

A

A secondary metabolite of Streptomyces bacteria.

209
Q

What does Antimycin A inhibit?

A

The transfer of electrons from heme bH to oxidized Q.

210
Q

Where does Antimycin A act?

A

At Qi site towards matrix side of complex 3.

211
Q

What is Atovaquone?

A

An anti malarial.

212
Q

What does Atovaquone inhibit?

A

The transfer of electrons from QH2 to iron sulphur complex.

213
Q

Where does Atovaquone inhibition process for electron occur?

A

At Qo site.

214
Q

Under what name is Atovaquone drug sold?

A

Under brand name: Mepron.

215
Q

For what is Atovaquone drug used?

A

To treat other parasitic diseases: Pneumocystis pneumonia.
Toxoplasmosis.
Babesia.

216
Q

What is pneumocystis pneumonia?

A

A type of pneumonia common in AIDS and kidney transplant patients.

217
Q

What is toxoplasmosis?

A

A disease caused by a parasite common in cats.

A zoonotic.

218
Q

What is babesia?

A

A tick borne parasite that infects livestock.

A zoonotic.

219
Q

What does ‘zoonotic’ mean?

A

It can be transferred from animals to humans.

220
Q

What are some other compounds that acts in a similar way by binding at Qo site?

A

Myxothiazol.

Stigmatellin.

221
Q

What is myxothiazol?

A

An antifungal agent.

222
Q

What is stigmatellin?

A

An antibiotic produced by myxobacteria.

223
Q

What happens when complex 3 is inhibited?

A

Proton motive force –> collapses.

Cell can longer make ATP to meet its needs.

224
Q

Why does the cell can no longer make ATP to meet its need after proton motive force collapses when complex 3 is inhibited?

A

Because there is no longer a head of protons able to rotate ATP synthase molecule.

225
Q

What occurs naturally from complex 3 when more electrons arrive than reducing ubiquinol?

A

Electron leakage.

226
Q

How are the electrons from complex 3 react when more electrons arrive?

A

Prematurely.
With molecular oxygen.
They produce superoxide free radical.

227
Q

What happens when ROS levels build up?

A

They can cause diseases driven by macromolecular damage and inflammation.

228
Q

What are ROS thought to be responsible for?

A

Aging.

229
Q

What does inhibition of complex 3 by antimycin A can cause?

A

The haem group –> ‘locked’ in reduced state –> re-oxidised.

230
Q

What does the lock of haem group to re-oxidised mean?

A

Electrons can’t be handed on from Qo.

They are transferred to oxygen instead.

231
Q

What can complex 3 inhibition cause?

A

ROS production at much higher levels than occurs naturally.

232
Q

What is the result if complex 3 is not functional?

A

Lethal.

233
Q

What are people with genetic abnormalities in complex 3?

A

Very rare.

234
Q

What are the characteristic of Biornstard syndrome?

A

Hearing loss.

Brittle hair.

235
Q

How many people are affected by Biornstard syndrome globally?

A

50 cases.

236
Q

For what is GRACILE syndrome stands for?

A

Growth Retardation, Aminoaciduria, Cholestasis, Iron overload, Lactic acidosis and Early death.

237
Q

How many people are globally affected by GRACILE syndrome?

A

30 cases.

238
Q

What are the causes of Biornstrad and GRACILE syndrome?

A

ROS build up + oxidative damage.

ATP lack.

239
Q

From what are milder conditions caused by?

A

Exercise intolerance.

240
Q

What happens in exercise intolerance?

A

Resting metabolism can be supported.

ATP cannot be generated fast enough.

241
Q

How is complex 4 called?

A

Cytochrome c oxidase (COX).

242
Q

Why is complex 4 called cytochrome c oxidase?

A

Because it oxidises cytochrome c handed on from complex 3.

243
Q

What is complex 4?

A

The final complex of ETC.

244
Q

By what is the reaction finished in ETC by complex 4?

A

By using H+ + molecular O2 : in mitochondrial matrix –> producing water.

245
Q

Where is complex bound?

A

In the inner mitochondrial membrane.

246
Q

By how many subunits is complex 4 made?

A

By 14 subunits.

247
Q

By what else is complex 4 made except from subunits?

A

Metal cofactors.
Two haems.
Two cytochromes.
Two copper clusters.

248
Q

Where are the 3 of the complex 4 subunits encoded?

A

In the mitochondrial DNA.

249
Q

By what are the 11 complex 4 subunits encoded?

A

By nuclear genes.

250
Q

Where are two haem molecules of complex 4 found?

A

In subunit 1.

251
Q

Where do the two haem molecules in complex 4 help?

A

In electron transport to subunit 2.

252
Q

What happens in subunit 2 of complex 4?

A

2 copper molecules receive and pass on electrons.

253
Q

How many electron does complex 4 receives from each of four cytochrome c molecules that have gained electrons from complex 3?

A

1 electron from each.

254
Q

What does complex 4 do with the electrons that receives from the 4 cytochrome c molecules?

A

It transfers them via 2 haem + 2 copper groups to –> 1 oxygen molecule.
It combines the oxygen with 4 H+ from mitochondrial lumen –> produce 2 water molecules.

255
Q

What does complex 4 pumps across membrane to inter membrane space?

A

4 H+.

256
Q

What the pumping of 4 H+ in the inter membrane space from complex 4 increases?

A

The electrochemical difference across membrane.

Membrane potential initiated by complex 1 and complex 3 actions.

257
Q

What does the adding to proton motive force by complex 4 help to maintain?

A

ATP synthesis.

258
Q

How can the adding to proton motive force by complex 4 maintain ATP synthesis?

A

By ensuring there is a head of protons in intermembrane space.

259
Q

Where is superoxide radical generated at complex 1?

A

In mitochondrial lumen.

260
Q

Where else is superoxide radical generated in mitochondrial lumen?

A

At complex 2.

261
Q

Where is superoxide released at complex 3?

A

On either side of the membrane.

262
Q

By which factor is superoxide released at complex 3?

A

By leakage of electrons from ubiquinone.

263
Q

Why is complex 4 not such an important site of electron leakage?

A

Because it is already handing electrons to molecular oxygen.

The leaks tend to happen before.

264
Q

Where can complex 4 inhibitors act?

A

On complex 4.

265
Q

When can inhibitors of complex 4 act on it?

A

When it is at one of the three different states that affect its conformation.

266
Q

What are the three states that affect the conformation of complex 4?

A
  1. Fully oxidized (pulsed).
  2. Partially reduced.
  3. Fully reduced.
267
Q

When does the fully pulsed state of complex 4 has highest activity?

A

When both haem a3 and one of the copper groups are oxidized.

268
Q

When does partially reduced state of complex 4 occur?

A

When receiving 2 electrons from cytochrome c has a shape that allows oxygen to bind.

269
Q

When does the fully reduced state occur?

A

When the enzyme is inactive.

270
Q

What do different inhibitors have for the different states of complex 4?

A

Different affinity.

271
Q

Where do cyanide, azide, and carbon monoxide act?

A

On complex 4?

272
Q

What inhibitors are cyanide, azide and carbon monoxide?

A

Non competitive inhibitors.

273
Q

Where do cyanide, azide and carbon monoxide bind on the complex 4?

A

Tightly on its active site.

274
Q

What happens to the oxygen levels when cyanide, azide and carbon monoxide inhibitors present on complex 4?

A

More oxygen is needed.

275
Q

Why more oxygen is needed when cyanide, azide and carbon monoxide inhibitors occur in complex 4?

A

To maintain cellular respiration.

276
Q

What are nitric oxide and hydrogen sulphide on complex 4?

A

Allosteric regulators of COX.

277
Q

Where does cyanide sit?

A

Between haem and copper groups.

278
Q

What is the function of cyanide in complex 4?

A

It prevents haem and copper groups from participating in redox reaction.
They can not receive electrons from cytochrome c.

279
Q

Where does cyanide inhibitor bind in complex 4?

A

It binds with high affinity in pulsed and partially reduced states.

280
Q

What are the consequences of cyanide binding on complex 4?

A

It produces chemical asphyxia.

Histotoxic hypoxia.

281
Q

What is histotoxic hypoxia?

A

A situation where oxygen is available but can’t be used.

282
Q

What can the swallow of a small quantity of solid cyanide or a cyanide solution of 200 mg or exposure to airborne cyanide of 270 ppm do to us?

A

Kill us in minutes.

283
Q

Why do spies have cyanide pills to take when captures to avoid interrrogation?

A

Because it can kill us in minutes.

284
Q

Are there any ante-dotes to cyanide?

A

Yes.

Need to be taken quickly.

285
Q

Why do ante-dotes of cyanide need to be taken quickly?

A

To rapidly produce a lot of ferric iron (FE3+) –> displace cyanide from cytochrome.

286
Q

Why ante-doted displace cyanide from cytochrome?

A

Because cyanide has a higher affinity for the ferric iron.

287
Q

What is the old method of displacing cyanide from cytochrome?

A

Inhalation of amyl nitrite.

Swallowing sodium nitrite + sodium thiosulphate.

288
Q

What will nitrites do?

A

Oxidise haemoglobin.

Produce methaemoglobin.

289
Q

Where does methaemoglobin bind?

A

To cyanide.

290
Q

What does the binding of methaemoglobin to cyanide comfort?

A

The COX enzyme binding.

291
Q

What is happening to the cyanide after it binds to methaemoglobin?

A

It is converted to an easily excretable form.
Removed by kidneys.
Peed out in urine.

292
Q

What does the more modern version of displacing cyanide from cytochrome avoid?

A

Messing with haemoglobin.

293
Q

What does haemoglobin do?

A

It creates oxygen delivery problems.

294
Q

What does the modern method of displacing cyanide from cytochrome uses instead of haemoglobin in order to not create oxygen delivery problems?

A

It uses hydroxocobalamin.

295
Q

Which is the cobalt used in the modern method of displacing cyanide from cytochrome?

A

The metal that moves cyanide.

296
Q

What can high nitric oxide concentration displace and comfort?

A

It can displace cyanide.

It can comfort cyanide’s effects.

297
Q

Are nitric oxide concentration levels high enough endogenously?

A

No.

298
Q

What does nitric oxide do?

A

It binds reversibly to metal groups.

Becomes reduced to –> nitrite.

299
Q

What can nitric oxide facilitate at low levels?

A

Oxygen delivery into deeper tissues.

300
Q

How can nitric oxide deliver oxygen into deeper tissues ate lower levels?

A

By slowing down the rate of activity in complex 4.

301
Q

What happens when the rate of activity in complex 4 is slowed down by nitric oxide?

A

Oxygen is not used up as fast.

Oxygen can diffuse further into tissue.

302
Q

What are carbon monoxide and hydrogen sulphide as inhibitors?

A

Non competitive.

303
Q

What do carbon monoxide and hydrogen sulphide produce?

A

Histotoxic hypoxia.

304
Q

Where does carbon monoxide bind?

A

To haemoglobin.

305
Q

What does carbon monoxide do once it binds to haemoglobin?

A

It disrupts its supply.

Disrupts oxygen use.

306
Q

Why is it really important to get boilers serviced, based on the carbon monoxide disruption of haemoglobin supply and oxygen use?

A

Because no one asphyxiates from fumes from incomplete combustion.

307
Q

What can ATP inhibit in complex 4?

A

The enzyme.

308
Q

Why does ATP inhibit the complex 4 enzyme?

A

To reduce the activity of electron transport chain.

309
Q

How does ATP act when it reduces the activity of electron transport chain because it inhibits the enzyme of complex 4?

A

As a negative feedback form.

310
Q

What does complete complex 4 inhibition reduces?

A

The proton motive force.

311
Q

Why is ROS generation not associated with complex 4?

A

Because ROS hands electrons to oxygen anyway.

All the ‘leaks’ in the system happen before this step.

312
Q

Which tissues have high metabolic rates?

A

Brain.
Heart.
Kidney.

313
Q

What are the tissues that have high metabolic rates most susceptible to?

A

Complex 4 inhibition or dysfunction.

314
Q

What are the defects in complex 4?

A

Fatal.

315
Q

What are the genetic abnormalities in complex 4?

A

Rare.

316
Q

Where do disorders of complex 4 manifest?

A

In early childhood.

317
Q

What do the disorders of complex 4 affect most severely?

A

The tissues with the highest metabolic rates.

318
Q

With what are the disorders of complex 4 associated?

A

With severe impairments.

319
Q

Where are the most often impairments in complex 4 diseases?

A

In genes.

320
Q

What do the genes do with the impairments in complex 4 diseases?

A

They control the meeting of complex.

321
Q

Which are the diseases of complex 4?

A 
Leigh syndrome.
Cardiomyopathy.
leukodystrophy.
anaemia.
deafness.
322
Q

From where does deafness occur in complex 4 diseases?

A

From impaired neural function.

323
Q

Where do patients experience lactic acidosis in complex 4 diseases?

A

Because, oxidative phosphorylation is impaired.

Pyruvate cannot be departed to mitochondria very quickly.

324
Q

What are the symptoms of Leigh disease?

A 
Damaged eye sight = Retinitis Pigmentosa.
Lactic acidosis.
Hypoglycaemia.
Aciduria.
Deafness.
Muscle tone lack.
Motor function loss.
Cognitive abilities.
Brain development impairment.
Speed failure.
Recurrent infections.
325
Q

Why is ‘hypoglycaemia’ a symptom of Leigh syndrome?

A

Because people with this syndrome rely heavily on glycolysis for ATP synthesis.

326
Q

What do the symptoms of Leigh syndrome highlight?

A

How the central normal electron transfer and ATP generation underpin health.

327
Q

What is ATP synthase?

A

One of the most ancient and highly conserved enzymes.

328
Q

Why is ATP synthase ancient and highly conserved?

A

Because its function is vital for life.

329
Q

Where do ATP hydrolysis and synthesis occur?

A

On three catalytic sites in F1 sector.

330
Q

Where does proton transport occur?

A

Through membrane-embedded Fo section.

331
Q

By how many subunits is Fo made?

A

8.

332
Q

Which are the subunits of Fo?

A

c-ring.

b subunits.

333
Q

Where is Fo section embedded?

A

In the membrane.

334
Q

By what subunits is F1 made?

A

α
β
γ
δ

335
Q

Where are proteins trapped as they cannot pass back through the inner mitochondrial membrane?

A

In the intermembrane space.

336
Q

Why can protons no pass back through the inner mitochondrial membrane on their own?

A

Because, the core of bilayer membrane is too hydrophobic for ions to get through large amounts.

337
Q

What do protons need to pass back through the inner mitochondrial membrane?

A

Help.
In the form of ATP synthase.
Complex 5.

338
Q

What is the formation of ATP from ADP?

A

Energetically favourable.

339
Q

Why is the formation of ATP from ADP energetically favourable?

A

Because, it requires energy input to add on phosphate group to ADP.

340
Q

What does ATP synthase do to drive the synthesis of ATP from ADP?

A

It traps the energy from the proton gradient.

341
Q

By bow many subunits does ATP synthesis consist?

A

2.

342
Q

Which are the 2 subunits of ATP synthesis?

A

Fo.

F1.

343
Q

What can F1 do?

A

Rotate in relation to Fo.

344
Q

What does Fo anchor?

A

In the membrane.

345
Q

What does the ability of F1 to rotate mean?

A

That it is a molecular machine/turbine.

346
Q

Though where do protons move?

A

Through a channel in Fo.

347
Q

Where do protons through Fo channel bind to?

A

To a ring on Fo.

348
Q

What does the proton binding to a ring on Fo cause?

A

Fo to rotate a notch.

349
Q

From where can protons exit after they bind to a ring on Fo and cause it to rotate a notch?

A

They exit from Fo into the lumen.

350
Q

What is the exit of protons from Fo into the lumen like?

A

Like a one way revolving door.

351
Q

Where are the protons then transferred after they exit from Fo into the lumen?

A

To the F1 subunit.

352
Q

By which factor are the protons transferred to F1 subunit?

A

By a central stalk that connects Fo + F1 subunits.

353
Q

What is the shape of the stalk that connects the Fo+F1 subunits of ATP synthase?

A

A cam shaft.

354
Q

What happens when the stalk that connects Fo+F1 subunits of ATP synthase rotate?

A

It squashes F1 subunit.

Causes conformational change in F1.

355
Q

By how many dimers is F1 made?

A

3.

356
Q

Where are the 3 dimers of F1 arranged?

A

In a ring.

357
Q

What happens in ATP synthesis total process then?

A 
ADP +Pi bind in gap between Fo+F1 subunits of ATP synthase.
Stalk rotates.
Fo+F1 squash together.
ADP+Pi squash together.
ADP+Pi fuse.
ADP+Pi form ATP.
358
Q

By which factors is the second rotation of the stalk driven?

A

By H+ movement through Fo.

359
Q

What does the other stalk rotation let happen?

A

Dimers pop apart again.
They release new formed ATP.
Allow ADP+Pi to bind again.

360
Q

What does keep the 2 dimers together in ATP synthase?

A

A flexible peripheral stalk.

361
Q

What the flexible peripheral stalk that holds the 2 dimers of ATP synthase allows?

A

The 2 dimers to flex with each rotation of the internal stalk.

362
Q

What gives the inner mitochondrial membrane its characteristic folds called cristae?

A

ATP synthase dimerization.

363
Q

What is the meaning of ATP synthase dimerization?

A

Proton gradient is focussed near ATP synthase –> makes the process highly efficient.

364
Q

What are the different classes of ATP synthase inhibitors?

A 
Peptide inhibitors.
Polyphenolic phytochemicals.
Polyketides.
Organotin compounds.
Polyenic α-pyrone derivatives.
Cationic inhibitors.
Substrate analogues.
Amino acid modifiers.
365
Q

Which antibiotics inhibit ATP synthase?

A

Efrapeptins.
Aurovertins.
Oligomycins.

366
Q

What do ‘efapeptins’ and ‘aurovertins’ inhibit?

A

ATP synthesis.

ATP hydrolysis.

367
Q

Where does ‘efrapeptins’ bind?

A

To ATP synthase at a site that extends from rotor.
Across central cavity of enzyme.
In the specific β-subunit catalytic site.

368
Q

What does the binding of ‘efrapeptins’ into β-subunit catalytic site of the enzyme prevent?

A

Closure of β subunit during rotation.

369
Q

Where do molecules of ‘aurovertin’ bind?

A

To the cleft between the nucleotide-binding and C-terminal domains of 2 β subunit domains.

370
Q

How does ‘oligomycin’ inhibit ATP synthase?

A

By binding in Fo sector.

Blocking proton conduction.

371
Q

Why is Fo called Fo?

A

Because, it binds oligomycin.

372
Q

What do the ATP synthesis inhibitors uncouple?

A

Oxidation from phosphorylation.

373
Q

What does the uncoupling of oxidation from phosphorylation mean?

A

Electron transfer works normally.
Protonmotive force remains intact.
Oxygen consumption occurs.
ROS generation occurs but is not used for ATP synthesis.

374
Q

What is ‘Rotenone’ ?

A

The most well known and used lab inhibitor of complex 1.

375
Q

What does ‘Carboxin’ inhibit?

A

Complex 2.

376
Q

What do ‘Antimycin A’ and ‘ Strobilurin’ impact?

A

Complex 3.

377
Q

By which factors is complex 4 inhibited?

A

By compounds like ‘ cyanide’ , ‘ phosphine’ , ‘nitric oxide’, ‘hydrogen sulphide’, ‘carbon monoxide’, ‘azide’.

378
Q

What does ATP exert?

A

Negative feedback on complex 4.

379
Q

By which factors are ATP synthase or complex 5 inhibited?

A

By ‘oligomycin’, ‘carbodiimide’, ‘diafenthurion’.

380
Q

What are the diseases of ATP synthase?

A

Rare.

381
Q

Why are the diseases of ATP synthase rare?

A

Because, ATP synthesis is vital to multicellular life.

382
Q

With what are the human neuromuscular disorders associated with?

A

Defects in ATP synthase.

383
Q

How many known mutations are in mitochondrial genes?

A

58.

384
Q

How many subunits encode mitochondrial genes?

A

8.

α of ATP synthase.

385
Q

How many distinct genetic mitochondrial dysfunction syndromes occur?

A

150.

386
Q

By which factor are genetic mitochondrial dysfunction syndromes caused by?

A

Reduced oxidative phosphorylation.

387
Q

How many human births are affected by genetic mitochondrial dysfunction syndromes?

A

1 in 5000.

388
Q

What are the typical symptoms of genetic mitochondrial dysfunction syndromes?

A 
Visual/hearing defects.
Encephalopathies.
Cardiomyopathies.
Myopathies.
Diabetes.
Dangerous liver and kidney function.
389
Q

To what are the mitochondrial genes sensitive?

A

To mutations.

390
Q

Why are mitochondrial genes sensitive to mutations?

A

Because, they are close to the sites of ROS production.

Mitochondrial genome has less developed repair systems than nuclear genome.

391
Q

What is FILA?

A

Fatal Infantile Lactic Acidosis.

392
Q

What is LHON?

A

Leber Hereditary Optic Neuropathy.

393
Q

What is MELAS?

A

Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like episodes.

394
Q

What is GRACILE?

A

Growth retardation Aminoaciduria Cholestasis Iron overload Lactic acidosis and Early death.

395
Q

What is MILS?

A

Maternally Inherited Leigh Syndrome.

396
Q

What is MLASA?

A

Mitochondrial myopathy Lactic Acidosis Sideroblastic Anemia.

397
Q

What do complex 1 mutations cause?

A 
Leigh Syndrome.
Leucoencepahlopathy.
FILA.
LHON.
MELAS.
398
Q

What do complex 2 mutations cause?

A

Leucoencephalopathy.

Hereditary tumours of neural crest.

399
Q

What do complex 3 mutations cause?

A

Leucoencephalopathy.
GRACILE.
Bjoornstad syndromes.

400
Q

What do complex 4 mutations cause?

A

Leigh syndrome.
Neonatal hepatopathy.
Cardiomyopathy.

401
Q

What do complex 5 mutations cause?

A 
Adult onset Neuropathy.
Ataxia.
Retinitis pigmentosa.
MILS.
MLASA.
Adult onset Cerebral ataxia.
Motor neurone syndrome.
402
Q

Where does dysfunction of different complexes lead?

A

To hypoglycaemia.
Lactic acidosis.
ROS damage.
Limited tissue function.

403
Q

By which factors are the complexes lead to sympotms?

A

By lack of efficient ATP generating capacity.
Lack of generation of proton motive force.
Inability to use force to drive ATP synthase.

404
Q

Where is the treatment of patients with complex mutations focuses?

A

On correcting acidosis or hypoglycaemia.

405
Q

What can the treatment of complex mutation’s symptoms not redress?

A

The issues of limited ATP synthesis.

High ROS production.

406
Q

What can be a way of correcting the problems of complex mutations?

A

Gene editing techniques.

407
Q

What is the disadvantage of using gene editing techniques to correct the problems of complex mutations?

A

It has a long way to go before it can be used clinically.

Medical Physiology (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions