This worksheet challenges students to complete the Krebs Cycle diagram by identifying key intermediates and energy carriers.

Let's solve this Krebs Cycle (Citric Acid Cycle) diagram step by step.

We are given a circular flow chart of the Krebs Cycle, with blank boxes to be filled in. The cycle starts with Acetyl-CoA combining with Oxaloacetic Acid to form Citrate, and then proceeds through a series of reactions, regenerating Oxaloacetic Acid at the end.

We have two lists:

- Left side: Molecules involved as inputs or intermediates.
- Right side: Molecules that are either substrates, products, or coenzymes.

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Step-by-step walkthrough of the Krebs Cycle:

1. Acetyl-CoA + Oxaloacetic Acid → Citrate
- Acetyl-CoA combines with oxaloacetate to form citrate.
- CoA is released.

2. Citrate → Isocitrate
- Citrate is isomerized to isocitrate.

3. Isocitrate → α-Ketoglutaric Acid
- Oxidation and decarboxylation: produces CO₂, NADH, and α-ketoglutarate.

4. α-Ketoglutaric Acid → Succinyl-CoA
- Oxidative decarboxylation: produces CO₂, NADH, and succinyl-CoA.

5. Succinyl-CoA → Succinate
- Substrate-level phosphorylation: produces ATP (or GTP), and releases CoA.

6. Succinate → Fumarate
- Oxidation: produces FADH₂.

7. Fumarate → Malate
- Hydration: adds water to form malate.

8. Malate → Oxaloacetate
- Oxidation: produces NADH and regenerates oxaloacetate.

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Now let’s fill in the blanks based on the flow.

We’ll go clockwise around the cycle starting from the top-left (where Acetyl-CoA enters).

Labeling the Boxes:

We'll identify each box in order:

1. Top box (starting point):
- Acetyl-CoA + Oxaloacetic Acid → Citrate
- So the large box here is Citrate

2. Next box after Citrate:
- Isocitrate

3. After Isocitrate:
- α-Ketoglutaric Acid

4. After α-Ketoglutaric Acid:
- Succinyl CoA

5. After Succinyl CoA:
- Succinic Acid

6. After Succinic Acid:
- Fumarate

7. After Fumarate:
- Malate

8. After Malate:
- Oxaloacetic Acid (regenerated)

Now, the small boxes around the cycle represent inputs/outputs (like NAD+, CO₂, ATP, etc.).

Let’s map them correctly.

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Mapping Inputs/Outputs:

- From Acetyl-CoA + Oxaloacetate → Citrate:
- Input: Acetyl-CoA, Oxaloacetic Acid
- Output: Citrate, CoA (released)
- So the small box next to Acetyl-CoA should be CoA (as it's released)

- From Isocitrate → α-Ketoglutarate:
- Produces: CO₂, NADH
- So small boxes: CO₂, NADH

- From α-Ketoglutarate → Succinyl-CoA:
- Produces: CO₂, NADH
- So: CO₂, NADH

- From Succinyl-CoA → Succinate:
- Produces: ATP, CoA
- So: ATP, CoA

- From Succinate → Fumarate:
- Uses: FAD, produces: FADH₂
- So: FAD, FADH₂

- From Fumarate → Malate:
- Adds H₂O

- From Malate → Oxaloacetate:
- Produces: NADH
- So: NADH

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Now fill in the diagram:

Let’s assign each blank:

Starting from the top-left and going clockwise:

1. Large box 1 (after Acetyl-CoA entry):
→ Citrate

2. Small box adjacent to Acetyl-CoA:
→ CoA (released when Acetyl-CoA donates acetyl group)

3. Next large box (after Citrate):
→ Isocitrate

4. Small boxes near Isocitrate → α-Ketoglutarate:
→ CO₂, NADH

5. Next large box:
→ α-Ketoglutaric Acid

6. Small boxes near α-Ketoglutarate → Succinyl-CoA:
→ CO₂, NADH

7. Next large box:
→ Succinyl CoA

8. Small boxes near Succinyl CoA → Succinate:
→ ATP, CoA

9. Next large box:
→ Succinic Acid

10. Small boxes near Succinate → Fumarate:
→ FAD, FADH₂

11. Next large box:
→ Fumarate

12. Small box near Fumarate → Malate:
→ H₂O

13. Next large box:
→ Malate

14. Small box near Malate → Oxaloacetate:
→ NADH

15. Final large box (regenerated):
→ Oxaloacetic Acid

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Final Answer – Fill in the Diagram:

Here’s how the boxes should be labeled:

#### Large boxes (intermediates):
1. Citrate
2. Isocitrate
3. α-Ketoglutaric Acid
4. Succinyl CoA
5. Succinic Acid
6. Fumarate
7. Malate
8. Oxaloacetic Acid

#### Small boxes (inputs/outputs):

- Near Acetyl-CoA: CoA (output)
- After Isocitrate: CO₂, NADH
- After α-Ketoglutarate: CO₂, NADH
- After Succinyl CoA: ATP, CoA
- After Succinate: FAD, FADH₂
- After Fumarate: H₂O
- After Malate: NADH

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Summary of Reactions:

| Step | Reaction | Products |
|------|--------|---------|
| 1 | Acetyl-CoA + Oxaloacetate → Citrate | CoA |
| 2 | Citrate → Isocitrate | None |
| 3 | Isocitrate → α-KG | CO₂, NADH |
| 4 | α-KG → Succinyl-CoA | CO₂, NADH |
| 5 | Succinyl-CoA → Succinate | ATP, CoA |
| 6 | Succinate → Fumarate | FADH₂ |
| 7 | Fumarate → Malate | H₂O |
| 8 | Malate → Oxaloacetate | NADH |

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✔ Answer Complete!

You can now fill the diagram as follows:

- Large boxes (clockwise):
1. Citrate
2. Isocitrate
3. α-Ketoglutaric Acid
4. Succinyl CoA
5. Succinic Acid
6. Fumarate
7. Malate
8. Oxaloacetic Acid

- Small boxes:
- After Acetyl-CoA: CoA
- After Isocitrate: CO₂, NADH
- After α-Ketoglutarate: CO₂, NADH
- After Succinyl CoA: ATP, CoA
- After Succinate: FAD, FADH₂
- After Fumarate: H₂O
- After Malate: NADH

This completes the Krebs Cycle diagram correctly.