Question

Identify the rate-limiting enzymes in CAC activity and detail the mechanism(s) by which these enzymes are regulated.

Answer 1

Isocitrate dehydrogenase is an oxidoreductase that catalyzes an oxidation reduction in which isocitrate is converted to alpha-ketoglutarate and CO2.

It is the first of four oxidative steps within the CAC and is the key rate-limiting step of the CAC.

The TCA cycle includes eight different steps:

1. The acetyl CoA joins with oxaloacetate to form citrate.

2. The citrate is then converted to isocitrate.

3. Isocitrate is then oxidised to alpha-ketoglutarate (a five carbon molecule) which results in the release of carbon dioxide. One NADH molecule is also formed in this step. Isocitrate dehydrogenase catalyzes this step and is rate limiting step as it is an allosterically controlled enzyme.

4. alpha-ketoglutarate is oxidised to form a 4 carbon molecule which picks up coenzyme A forming succinyl CoA.

5. Succinyl CoA is then converted to succinate and one GTP molecule is produced.

6. Succinate is converted into fumarate and a molecule of FADH₂ is produced.

7. Fumarate is converted to malate.

8. Malate is then converted into oxaloacetate and NADH is also produced.