S2) Energy Production II — TCA Cycle & ETC Flashcards

1
Q

Describe the structure of the mitochondrion

A
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2
Q

Pyruvate from Stage 1 (glycolysis) does not enter directly into Stage 3 (TCA cycle).

What reaction occurs?

A

The link reaction

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3
Q

Where does the link reaction occur?

A

Mitochondrial matrix – pyruvate transported from cytoplasm across mitochondrial membrane

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4
Q

Which enzyme catalyses the link reaction?

A

Pyruvate dehydrogenase (large multi-enzyme complex)

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5
Q

Describe three features of the link reaction

A
  • Reaction is sensitive to Vitamin B1 deficiency (PDH requires factors from B1)
  • Reaction is irreversible (key regulatory step)
  • Irreversible loss of CO2
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6
Q

PDH is subject to multiple regulation.

Describe its activation and inhibition in terms of phosphorylation and dephosphorylation

A
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7
Q

What is the consequence of PDH deficiency?

A

Lactic acidosis

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8
Q

Describe three features of the Tricarboxylic Acid Cycle

A
  • Acetyl CoA converted to 2CO2
  • Oxidative
  • Produces some energy & precursors for biosynthesis
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9
Q

Where does the TCA cycle occur?

A

Mitochondria

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10
Q

How many rounds of TCA cycle occur per glucose molecule entering from glycolysis?

A
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11
Q

What is produced after the two rounds of the TCA cycle occurring per glucose molecule?

A
  • 6 NADH
  • 2 FADH2
  • 2 GTP
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12
Q

How is the TCA cycle regulated?

A
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13
Q

Appreciate the biological precusors molecules synthesised from the TCA cycle

A
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14
Q

Which three events occur in oxidative phosphorylation?

A
  • Electron transport and ATP synthesis
  • NADH & FADH2 re-oxidised
  • Large amounts of energy (ATP) produced
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15
Q

Where does the ETC occur?

A

Inner mitochondrial membrane

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16
Q

What is the role of the electron carriers NADH and FAD2H in the ETC?

A
  • NADH and FAD2H contain high energy electrons that can be transferred to O2 through a series of carrier molecules with the release of large amounts of energy
  • The energy is used to drive ATP synthesis in the final stage of catabolism (oxidative phosphorylation)
17
Q

Identify and describe the two uses of reducing power in ATP synthesis

A
  • Electron transport: electrons on NADH and FAD2H transferred through a series of carrier molecules to oxygen
  • Oxidative phosphorylation: free energy released used to drive ATP synthesis
18
Q

Describe what happens in the ETC

A
  • NADH and FADH2 supply electrons from metabolic substrates
  • Electrons pass through the ETC and reduce oxygen to form H2O at Complex IV
19
Q

What do proton translocating complexes do?

A
  • Complexes I, III and IV act as proton translocating complexes
  • They use free energy derived from ETC to move protons from the inside to the outside of the inner mitochondrial membrane to build up a proton motive force
20
Q

Explain the concept of the proton motive force

A
  • The inner mitochondrial membrane is impermeable to protons and the H+ concentration in the intermembrane space builds up
  • A [H+] gradient (membrane potential) across inner mitochondrial membrane forms i.e. the proton motive force
21
Q

Oxidative phosphorylation involves electron transport coupled to ATP synthesis.

In three steps, explain how this occurs

A

⇒ Electrons are transferred from NADH and FAD2H to molecular oxygen

⇒ Energy released is used to generate the PMF

⇒ Energy from the dissipation of the proton motive force is coupled to the synthesis of ATP from ADP

22
Q

How many proton translocating complexes are used by NADH and FADH2 respectively?

A

Electrons in NADH have more energy than in FAD2H:

  • NADH uses 3 PTCs
  • FADH2 uses only 2 PTCs
23
Q

State the amounts of ATP synthesised from the oxidation of two moles of NADH and FADH2 respectively

A
  • Oxidation of 2 moles of NADH → synthesis of 5 moles of ATP (P/O = 2.5)
  • Oxidation of 2 moles of FADH2 → synthesis of 3 moles of ATP (P/O = 1.5)
24
Q

In 4 steps, explain how a high [ATP] regulates oxidative phosphorylation

A

⇒ Low [ADP] is low means no substrate for ATP synthase

⇒ Inward flow of H+ stops

⇒ [H+] in intermitochondrial space increases

⇒ Stops electron transport

25
Q

Explain the inhibition of oxidative phosphorylation

A

Inhibitors block electron transport e.g. cyanide prevents acceptance of electrons by O2

26
Q

In three steps, explain how the uncoupling of oxidative phosphorylation occurs

A

⇒ Uncouplers increase the permeability of inner mitochondrial membrane to H+

⇒ Dissipate proton gradient (reducing PMF)

⇒ No drive for ATP synthesis

27
Q

Identify an example of an uncoupler

A

Fatty acids

28
Q

Thermogenin (UCP1) is a naturally-occurring uncoupling protein found in brown adipose tissue.

In 6 steps, explain its role in response to cold

A

Noradrenaline activates lipase

⇒ Lipase releases fatty acids from triacylglycerol

⇒ Fatty acids activate UCP1

⇒ UCP1 uncouples electron transport from ATP synthesis

H+ are transported back into mitochondria

⇒ Energy of PMF is released as extra heat

29
Q

Where is brown adipose tissue found and what is its function?

A
  • Newborn infants – to maintain heat, particularly around vital organs
  • Hibernating animals – to generate heat to maintain body temperature
30
Q

Compare and contrast oxidative phosphorylation with substrate level phosphorylation in terms of the following:

  • Requirements
  • Energy coupling
  • O2 dependency
  • ATP synthesis
A