Rate Controlling Steps of the TCA Cycle

Question 1

Which 3 enzymes appear to be controllers of the TCA cycle based on their Gibbs Free Energy?

Answer 1

1) Citrate synthase
2) Isocitrate dehydrogenase
3) alpha-Ketoglutarate dehydrogenase

Question 2

True or false: The TCA cycle is not very active in heart muscle.

Answer 2

False; it is quite active.

Question 3

What is the flux of the TCA cycle in heart muscle proportional to?

Answer 3

Rate of cellular O2 consumption

Question 4

How do we know that the TCA Cycle is regulated by feedback mechanisms that coordinate NADH production with energy expenditure?

Answer 4

Because O2 consumption, NADH reoxidation, and ATP production are tightly coupled.

Question 5

What are the three types of regulation of the enzymes of the TCA Cycle?

Answer 5

1) Substrate availability
2) Product inhibition
3) Competitive feedback inhibition

Question 6

What are the two most crucial types of regulators of the TCA Cycle?

Answer 6

1) It’s substrates: acetyl CoA and oxaloactate

2) It’s product: NADH

Question 7

With what other molecule does the concentration of oxaloacetate exist in equilibrium with?

Answer 7

malate

Question 8

What must a change in [NADH] be accompanied by to keep K the same? Why?

Answer 8

A change in [oxaloacetate]; because K = [oxaloacetate][NADH] / [malate][NAD+].

Question 9

What happens to mitochondrial [NADH] and [oxaloacetate] if muscle workload and respiration rate increase?

Answer 9

[NADH] goes down, causing [oxaloacetate] to go up to maintain K. This activates the TCA-Cycle (substrate availability).

Question 10

What is the most important controller of the TCA Cycle?

Answer 10

NADH (increased [NADH] inhibits TCA Cycle, decreased [NADH] activates TCA cycle.

Question 11

True or false: The concentrations of acetyl-CoA and oxaloacetate are enough to saturate citrate synthase.

Answer 11

False.

Question 12

What makes regulation of the TCA Cycle unique?

Answer 12

It is largely dependent on substrate availability.

Question 13

True or false: Aconitase is an important rate controlling enzyme in the TCA Cycle?

Answer 13

False; it operates near equilibrium

Question 14

What does the rate of citrate consumption depend on?

Answer 14

The activity of isocitrate dehydrogenase, which is activated by NAD+ and strongly inhibited by NADH.

Question 15

What is citrate synthase inhibited by?

Answer 15

1) Citrate (product: competitive inhibitor)

2. Succinyl CoA: competitive inhibitor of acetyl-CoA.

Question 16

What is alpha-ketoglutarate controlled by?

Answer 16

1) NADH is a feedback inhibitor.
2) Succinyl CoA
3) Ca2+ (activator)

Question 17

What controls isocitrate dehydrogenase?

Answer 17

1) NAD+ (activator)
2) NADH (inhibitor)
3) ADP (allosteric activator)
4) ATP (inhibitor)
5) Ca2+ (activator)

Question 18

What two important physiological responses does Ca2+ stimulate in muscle?

Answer 18

1) Contractions

2) Production of ATP to fuel muscle contractions.

Question 19

How does Ca2+ contribute to the availability of ATP to fuel muscle contractions?

Answer 19

1) It activates pyruvate dehydrogenase phosphatase, which activates pyruvate dehydrogenase, generating acetyl CoA for the TCA Cycle.
2) It also activates isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase.

Question 20

Which enzymes in the TCA Cycle are inhibited by NADH?

Answer 20

1) Pyruvate dehydrogenase
2) Citrate synthase
3) Isocitrate dehydrogenase
4) Alpha-ketoglutarate dehydrogenase

Question 21

Which enzymes in the TCA cycle are stimulated by Ca2+?

Answer 21

1) Pyruvate dehydrogenase
2) Isocitrate dehydrogenase
3) Alpha-ketoglutarate dehydrogenase

Question 22

Which enzyme in the TCA cycle is activated by ADP?

Answer 22

Isocitrate dehydrogenase

Question 23

Which other metabolic pathways use TCA Cycle intermediates?

Answer 23

1) Glucose biosynthesis via gluconeogenesis
2) Fatty acid biosynthesis
3) Amino acid biosynthesis (using oxaloacetate and alpha-ketoglutarate)

Question 24

Which pathways replenish TCA Cycle intermediates?

Answer 24

Pyruvate to oxaloacetate

Question 25

Which TCA Cycle intermediates are used for Fatty Acid Biosynthesis?

Answer 25

Citrate

Question 26

Which TCA Cycle intermediates are used for Glucose biosynthesis via gluconeogenesis?

Answer 26

Malate and oxaloacetate

Question 27

Which TCA Cycle intermediates are used for the synthesis of porphyrins?

Answer 27

succinyl CoA

Question 28

Which TCA Cycle Intermediates are used for the synthesis of cholesterol?

Answer 28

Citrate