The TCA Cycle

Question 1

To be fully oxidised, substrates must enter the TCA cycle as a particular molecule - what is that molecule?

Answer 1

Acetyl-CoA

Question 2

Where does the TCA cycle take place

Answer 2

In the mitochondria (matrix)

Question 3

The TCA cycle is a series of what kind of reactions

Answer 3

Oxidative reactions

Question 4

What is the first intermediate in the TCA cycle, and what is its significance?

Answer 4

Citrate. It is a branch-point and a point of feedback.

If there is a build-up of citrate, it indicates the cycle is not proceeding appropriately (the cell has enough/too much energy). Citrate will inhibit its own enzyme (citrate synthase) to slow production.

If citrate is not being converted sufficiently, it will be diverted to the cytoplasm for fatty acid synthesis.

Question 5

What is the start and end-point of the TCA cycle?

Answer 5

Oxaloacetate (OAA). It binds with ATP to produce citrate, and in the final step, is the product after malate liberates NADH and H+.

Question 6

What is the main benefit (products/intermediates) of the TCA cycle?

Answer 6

It produces three NADH and one FADH2 per turn (with two turns per glucose). It also produces one GTP, which becomes ATP through substrate-level phosphorylation.

Question 7

What effect does ATP have on the TCA cycle?

Answer 7

It allosterically stimulates citrate synthase and iso-citrate dehydrogenase, allowing the cycle to proceed much faster.

Question 8

High levels of which compounds will inhibit the TCA cycle?

Answer 8

ATP (inhibits citrate synthase and iso-citrate dehydrogenase). Excess NADH will also inhibit the cycle (both relate to the cell redox state - highly reduced).

High [succinyl-CoA] will feed-back on its own enzyme to inhibit the cycle.

Question 9

What is the Committed Step of the TCA Cycle

Answer 9

When iso-citrate dehydrogenase catalyses iso-citrate to become alpha KG.

Question 10

There are five broad forms of regulation in the TCA cycle - what are they?

Answer 10

1. Substrate availability (acetyl-CoA)
2. Committed step - isocitrate to alpha KG
3. Metabolic Branch Points - citrate can continue in the cycle or be returned to the cytoplasm to make fatty acids
4. Feedback/forward loops - High citrate or succinyl-CoA levels inhibit their respective enzymes.
5. Cellular Energy Levels - ATP/ADP (also NADH/NAD) levels have allosteric regulation over enzymes at the committed step and at the entry point.

Question 11

The TCA cycle does not just produce energy. It is also a hub-point for other metabolic pathways. What other products can be made?

Answer 11

Products can be spun off for -

1. Fatty Acid Synthesis (via citrate)
2. Glucose Synthesis (if no acetyl-CoA is entering, pyruvate may be used).
3. Amino Acid Synthesis (from excess alpha-KG and OAA)
4. Porphyrin synthesis (from succinyl-CoA)