Regulation of citric acid cycle Flashcards

1
Q

Which enzymes are the citric acid rate-controlling enzymes

A
  1. Citrate synthase
  2. isocitrate dehydrogenase
  3. 2-oxoglutarate dehydrogenase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the three main ways enzymes in the citric cycle are regulated

A
  1. Substrate availability
  2. product inhibition
  3. competitive feedback inhibition by intermediates further along the cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How do the substrates regulate citric acid cycle

A
  1. Acetyl-CoA and oxaloacetate are not present in mitochondria in concentrations that would staurate citrate synthase
  2. Therefore metabolic flux varies with substrate concentration and availability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is the production of acetyl-CoA regulated

A
  1. Activity of pyruvate dehydrogenase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is oxaloacetate concentration regulated

A
  1. In equilibrium with malate
  2. its concentration fluctuates with NADH/NAD+ concentration ratio
  3. k= [oxaloacetate][NADH]/[malate][NAD+]
  4. As respiration rate increases [NADH] decreases
  5. This means [oxaloacetate] increases which stimulates the citrate synthase reaction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the role of NAD+

A
  1. [citrate] falls as wokr increases, indicating the rate of citrate removal increases more than its formation
  2. The rate of citrate removal is controlled by NAD+-dependent-isocitrate dehydrogenase
  3. Citrate synthase also inhibited by NADH
  4. NAD+-dependent-isocitrate dehydrogenase is more sensitive to [NADH] changes than citrate synthase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens when [citrate] falls upon transition from low to high work and respiration rates

A
  1. citrate is a competitive inhibitor of oxaloacetate for citrate synthase
  2. the fall of [citrate] caused by increased isocitrate dehydrogenase activity increases the rate of citrate formation
  3. 2-oxoglutarate dehydrogenase is also strongly inhibited by its products, NADH and succinyl-CoA. Its activity increases when [NADH] decreases
  4. Succinate thiokinase also competes with acetyl-CoA in the citrate synthase reaction
  5. These interlocking system keeps the citric acid cycle coordinately regulated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are allosteric regulators of citric acid cycle enzymes

A
  1. ADP
  2. ATP
  3. Ca2+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does [ADP] and [ATP] affect citric cycle

A
  1. Increased workload is accompanied by increased [ADP], resulting from increased rate of ATP hydrolysis
  2. ADP acts as an allosteric activator of isocitrate dehydrogenase by decreasing its Km for isocitrate
  3. ATP which builds up when muscle is at rest inhibits the enzyme
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does Ca2+ affect citric acid cycle

A
  1. Ca2+ activates pyruvate dehydrogenase phosphatase which activates pyruvate dehydrogenase complex to produce acetyl-CoA
  2. It also activates both isocitrate dehydrogenase and oxoglutarate dehydrogenase
  3. The same signal stimulates muscle contraction and the production of ATP to fuel it
How well did you know this?
1
Not at all
2
3
4
5
Perfectly