Kreb's Cycle

1. Formation of Citrate

• Reaction: Acetyl-CoA (2C) combines with oxaloacetate (4C) to form citrate (6C).

• Enzyme: Citrate synthase.

• By-products: CoA-SH (coenzyme A is released).

2. Conversion of Citrate to Isocitrate

• Reaction: Citrate is isomerized into isocitrate through an intermediate called cis-aconitate.

• Enzyme: Aconitase.

• Mechanism: This is a two-step reaction involving dehydration and rehydration.

3 Oxidation of Isocitrate to Alpha-Ketoglutarate

• Reaction: Isocitrate is oxidized to α-ketoglutarate (5C), producing NADH and releasing CO₂.

• Enzyme: Isocitrate dehydrogenase.

• By-products: NADH and CO₂.

• Key Point: This is the first oxidative decarboxylation step in the cycle.

4. Oxidation of Alpha-Ketoglutarate to Succinyl-CoA

• Reaction: α-Ketoglutarate is oxidized and combined with CoA to form succinyl-CoA (4C).

• Enzyme: α-Ketoglutarate dehydrogenase complex.

• By-products: NADH and CO₂.

• Key Point: This is the second oxidative decarboxylation step in the cycle.

5. Conversion of Succinyl-CoA to Succinate

• Reaction: Succinyl-CoA is converted to succinate (4C), coupled with the phosphorylation of GDP to GTP (or ADP to ATP).

• Enzyme: Succinyl-CoA synthetase (succinate thiokinase).

• By-products: GTP (or ATP) and CoA-SH.

6. Oxidation of Succinate to Fumrate

• Reaction: Succinate is oxidized to fumrate (4C).

• Enzyme: Succinate dehydrogenase.

• By-products: FADH₂.

• Key Point: This enzyme is embedded in the inner mitochondrial membrane and part of the electron transport chain (ETC).

7. Hydration of Fumarate to Malate

• Reaction: Fumarate is hydrated to form malate (4C).

• Enzyme: Fumarase (fumarate hydratase).

• Mechanism: Addition of water across the double bond.

8. Oxidation of Malate to Oxaloacetate

• Reaction: Malate is oxidized to regenerate oxaloacetate (4C).

• Enzyme: Malate dehydrogenase.

• By-products: NADH.

• Key Point: The cycle is now ready to start again with the addition of another acetyl-CoA.

Citrate synthase

1. ________

2. Aconitase

3. Isocitrate dehydrogenase

4. Alpha-Ketoglutarate dehydrogenase complex

5. Succinyl-CoA synthase

6. Succinate dehydrogenase

7. Fumrase

8. Malate dehydrogenase

Aconitase

1. Citrate synthase

2. _____

3. Isocitrate dehydrogenase

4. α-Ketoglutarate dehydrogenase complex

5. Succinyl-CoA synthase

6. Succinate dehydrogenase

7. Fumrase

8. Malate dehydrogenase

Isocitrate dehydrogenase

1. Citrate synthase

2. Aconitase

3. ________

4. Alpha-Ketoglutarate dehydrogenase complex

5. Succinyl-CoA synthase

6. Succinate dehydrogenase

7. Fumrase

8. Malate dehydrogenase

Alpha-Ketoglutarate dehydrogenase complex

1. Citrate synthase

2. Aconitase

3. Isocitrate dehydrogenase

4. _________

5. Succinyl-CoA synthase

6. Succinate dehydrogenase

7. Fumrase

8. Malate dehydrogenase

Succinyl-CoA synthase

1. Citrate synthase

2. Aconitase

3. Isocitrate dehydrogenase

4. Alpha-Ketoglutarate dehydrogenase complex

5. ________

6. Succinate dehydrogenase

7. Fumrase

8. Malate dehydrogenase

Succinyl-CoA synthase

1. Citrate synthase

2. Aconitase

3. Isocitrate dehydrogenase

4. Alpha-Ketoglutarate dehydrogenase complex

5. ______

6. Succinate dehydrogenase

7. Fumrase

8. Malate dehydrogenase

Fumrase

1. Citrate synthase

2. Aconitase

3. Isocitrate dehydrogenase

4. Alpha-Ketoglutarate dehydrogenase complex

5. Succinyl-CoA synthase

6. Succinate dehydrogenase

7. _______

8. Malate dehydrogenase

Malate dehydrogenase

1. Citrate synthase

2. Aconitase

3. Isocitrate dehydrogenase

4. Alpha-Ketoglutarate dehydrogenase complex

5. Succinyl-CoA synthase

6. Succinate dehydrogenase

7. Fumrase

8. __________