2. Oxidative Phosphorylation And The ETC Flashcards

1
Q

Which 2 process allow the use of reducing power in ATP synthesis?

A
  1. Electrons on NADH and FADH2 transferred through a series of carrier molecules to oxygen - ELECTRON TRANSPORT
  2. Free energy released in ETC used to drive ATP synthesis - OXIDATIVE PHOSPHORYLATION
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2
Q

Where does the ETC occur?

A

Inner mitochondrial membrane

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3
Q

What is the function of NADH in the ETC?

A
  1. NADH is oxidised to NAD+, releasing 2e-.
  2. Movement of 2e- between the carriers of the ETC until it combines with 1/2 O2 and 2H+ to produce H2O.
  3. This movement pumps protons across the inner MT membrane into the intermembrane space (pumping out of 10 H+ in total for 1 NADH) - forms H+ gradient.
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4
Q

What is the function of FADH2 in the ETC?

A
  1. FADH2 is oxidised to FAD+, releasing 2e-.
  2. Movement of 2e- between the carriers of the ETC until it combines with 1/2 O2 and 2H+ to produce H2O.
  3. This movement pumps protons across the inner MT membrane into the intermembrane space (pumping out of 6H+ in total for 1 FADH2) - forms H+ gradient.
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5
Q

In oxidative phosphorylation, what happens to the protons pumped into the intermembrane space? What does this produce?

A

Flow back down their concentration gradient into the MT matrix via ATP synthetase.

For every 4 H+, 1 ATP is produced (so 1 NADH = 2.5 ATP, 1 FADH2 = 1.5 ATP).

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6
Q

What is the proton motive force?

A

The [H+] gradient across the inner mitochondrial membrane

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7
Q

Why does NADH produce more ATP than FADH2?

A

NADH electrons have more energy so use 3 proton transport complexes whilst FADH2 uses only 2.

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8
Q

What regulates the process of oxidative phosphorylation?

A

[ATP] and [ADP]

  1. When [ATP] is high, there is low [ADP]… so no substrate for ATP synthase.
  2. Inward flow of H+ stops… [H+] in intermitochondrial space increases.
  3. Prevents further H+ pumping… stops electron transport and therefore oxidative phosphorylation.

Opposite when low [ATP].

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9
Q

What is the difference between inhibition and uncoupling of oxidative phosphorylation?

A

Inhibitors

  1. block electron transport…
  2. so no proton motive force…
  3. so no oxidative phosphorylation…
  4. lethal.

Uncouplers:

  1. increase the permeability of the mitochondrial inner membranes to protons…
  2. so H+ enter mitochondria without driving ATP synthetase… dissipates proton motive force…
  3. so no oxidative phosphorylation despite continued ETC.
  4. PMF dissipated as heat rather than ATP.
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10
Q

Give examples of electron transport inhibitors.

A

Carbon monoxide

Cyanide: prevents acceptance of electrons by oxygen

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11
Q

Give examples of oxidative phosphorylation uncouplers.

A

Dinitrophenol, dinitrocresol, fatty acids

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12
Q

What are oxidative phosphorylation diseases?

A

Genetic defects in proteins encoded by mtDNA (some subunits of the PTCs and ATP synthase), resulting in decreased electron transport and ATP synthesis.

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13
Q

What is the role of uncoupling proteins (UCPs)?

A

Specific proteins whose function is to uncouple the ETC from ATP production to produce heat.

UCP1-5 are located on inner mitochondrial membrane and allow a lead of protons across the membrane, reducing the PMF and inhibiting ATP synthesis.

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14
Q

What is the specific role of UCP1?

A

Expressed in brown adipose tissue and is involved in non-shivering thermogenesis.

  1. In response to cold, noradrenaline activates lipolysis.
  2. Lipase releases fatty acids from triacylglycerol to provide fuel for oxidation in brown adipose tissue.
  3. Beta-oxidation of fatty acids produces NADH and FADH2, driving ETC and increasing PMF.
    BUT
  4. Noradrenaline also activates UCP1 allowing the protons to re-enter the MT matrix without driving ATP synthesis.
  5. PMF is dissipated as heat rather than ATP.
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15
Q

What is the consequence of patient poisoning by uncoupling agents such as dinitrocresol?

A

Currently no antidote to these poisons, can lead to death.

Death can sometimes be avoided by physical cooling, haemoperfusion and intravenous antioxidants such as glutathione.

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16
Q

Compare oxidative phosphorylation and substrate level phosphorylation.

A

Oxidative phosphorylation

  1. Requires membrane-associated complexes (inner mitochondrial membrane)
  2. Energy coupling occurs indirectly through generation and subsequent utilisation of a PMF
  3. Cannot occur in absence of O2
  4. Major process for ATP synthesis in cells requiring large amounts of energy

Substrate level phosphorylation

  1. Requires soluble enzymes (cytoplasmic and MT matrix)
  2. Energy coupling occurs directly through formation of high energy of hydrolysis bond (phosphoryl-group transfer)
  3. Can occur to a limited extent in absence of O2
  4. Minor process for ATP synthesis in cells requiring large amounts of energy