Rate Controlling Steps of the TCA Cycle Flashcards
Which 3 enzymes appear to be controllers of the TCA cycle based on their Gibbs Free Energy?
1) Citrate synthase
2) Isocitrate dehydrogenase
3) alpha-Ketoglutarate dehydrogenase
True or false: The TCA cycle is not very active in heart muscle.
False; it is quite active.
What is the flux of the TCA cycle in heart muscle proportional to?
Rate of cellular O2 consumption
How do we know that the TCA Cycle is regulated by feedback mechanisms that coordinate NADH production with energy expenditure?
Because O2 consumption, NADH reoxidation, and ATP production are tightly coupled.
What are the three types of regulation of the enzymes of the TCA Cycle?
1) Substrate availability
2) Product inhibition
3) Competitive feedback inhibition
What are the two most crucial types of regulators of the TCA Cycle?
1) It’s substrates: acetyl CoA and oxaloactate
2) It’s product: NADH
With what other molecule does the concentration of oxaloacetate exist in equilibrium with?
malate
What must a change in [NADH] be accompanied by to keep K the same? Why?
A change in [oxaloacetate]; because K = [oxaloacetate][NADH] / [malate][NAD+].
What happens to mitochondrial [NADH] and [oxaloacetate] if muscle workload and respiration rate increase?
[NADH] goes down, causing [oxaloacetate] to go up to maintain K. This activates the TCA-Cycle (substrate availability).
What is the most important controller of the TCA Cycle?
NADH (increased [NADH] inhibits TCA Cycle, decreased [NADH] activates TCA cycle.
True or false: The concentrations of acetyl-CoA and oxaloacetate are enough to saturate citrate synthase.
False.
What makes regulation of the TCA Cycle unique?
It is largely dependent on substrate availability.
True or false: Aconitase is an important rate controlling enzyme in the TCA Cycle?
False; it operates near equilibrium
What does the rate of citrate consumption depend on?
The activity of isocitrate dehydrogenase, which is activated by NAD+ and strongly inhibited by NADH.
What is citrate synthase inhibited by?
1) Citrate (product: competitive inhibitor)
2. Succinyl CoA: competitive inhibitor of acetyl-CoA.
What is alpha-ketoglutarate controlled by?
1) NADH is a feedback inhibitor.
2) Succinyl CoA
3) Ca2+ (activator)
What controls isocitrate dehydrogenase?
1) NAD+ (activator)
2) NADH (inhibitor)
3) ADP (allosteric activator)
4) ATP (inhibitor)
5) Ca2+ (activator)
What two important physiological responses does Ca2+ stimulate in muscle?
1) Contractions
2) Production of ATP to fuel muscle contractions.
How does Ca2+ contribute to the availability of ATP to fuel muscle contractions?
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.
Which enzymes in the TCA Cycle are inhibited by NADH?
1) Pyruvate dehydrogenase
2) Citrate synthase
3) Isocitrate dehydrogenase
4) Alpha-ketoglutarate dehydrogenase
Which enzymes in the TCA cycle are stimulated by Ca2+?
1) Pyruvate dehydrogenase
2) Isocitrate dehydrogenase
3) Alpha-ketoglutarate dehydrogenase
Which enzyme in the TCA cycle is activated by ADP?
Isocitrate dehydrogenase
Which other metabolic pathways use TCA Cycle intermediates?
1) Glucose biosynthesis via gluconeogenesis
2) Fatty acid biosynthesis
3) Amino acid biosynthesis (using oxaloacetate and alpha-ketoglutarate)
Which pathways replenish TCA Cycle intermediates?
Pyruvate to oxaloacetate
