Draw the Krebs cycle and explain each step with enzymes involved

Question

Draw the Krebs cycle (citric acid cycle/TCA cycle) and explain each step with the enzymes involved, substrates, and products.

Solution — Step by Step

flowchart TD
    A[Acetyl CoA + Oxaloacetate] -->|Citrate synthase| B[Citrate 6C]
    B -->|Aconitase| C[Isocitrate 6C]
    C -->|Isocitrate dehydrogenase| D[Alpha-ketoglutarate 5C]
    D -->|Alpha-ketoglutarate dehydrogenase| E[Succinyl CoA 4C]
    E -->|Succinyl CoA synthetase| F[Succinate 4C]
    F -->|Succinate dehydrogenase| G[Fumarate 4C]
    G -->|Fumarase| H[Malate 4C]
    H -->|Malate dehydrogenase| I[Oxaloacetate 4C]
    I --> A
    C -->|CO2 + NADH| D
    D -->|CO2 + NADH| E
    E -->|GTP| F
    F -->|FADH2| G
    H -->|NADH| I

The 2C acetyl group from Acetyl CoA combines with 4C oxaloacetate (OAA) to form 6C citrate. Enzyme: citrate synthase. This is a condensation reaction — CoA is released. This is the entry point of the cycle.

Citrate is rearranged to isocitrate via an intermediate (cis-aconitate). Enzyme: aconitase. This involves dehydration followed by rehydration — the hydroxyl group shifts position.

Isocitrate (6C) is oxidatively decarboxylated to alpha-ketoglutarate (5C). Enzyme: isocitrate dehydrogenase. Products: 1 CO $_2$ released + 1 NADH produced. This is the first carbon lost as CO $_2$ .

Alpha-ketoglutarate (5C) is oxidatively decarboxylated to succinyl CoA (4C). Enzyme: alpha-ketoglutarate dehydrogenase complex. Products: 1 CO $_2$ released + 1 NADH. This step is irreversible and is the rate-limiting step.

Succinyl CoA is converted to succinate with release of CoA. Enzyme: succinyl CoA synthetase. The energy released is used to produce 1 GTP (which converts to ATP). This is the only substrate-level phosphorylation in the Krebs cycle.

Succinate is oxidised to fumarate. Enzyme: succinate dehydrogenase (the only enzyme embedded in the inner mitochondrial membrane). Product: 1 FADH $_2$ . This is the only step that produces FADH $_2$ instead of NADH.

Fumarate is hydrated to malate. Enzyme: fumarase. Water is added across the double bond.

Malate is oxidised to oxaloacetate (OAA). Enzyme: malate dehydrogenase. Product: 1 NADH. OAA is now ready to accept another acetyl CoA, restarting the cycle.

Why This Works

The Krebs cycle systematically dismantles the 2-carbon acetyl group by oxidising it to 2 CO $_2$ while capturing the released energy as reduced coenzymes (3 NADH + 1 FADH $_2$ ) and 1 GTP. These coenzymes then carry electrons to the ETC, where the bulk of ATP is produced.

Net yield per turn: 3 NADH + 1 FADH $_2$ + 1 GTP + 2 CO $_2$ . Since each glucose gives 2 acetyl CoA, multiply by 2 for the full glucose oxidation.

Common Mistake

Students forget that the Krebs cycle runs twice per glucose molecule (because one glucose produces 2 pyruvate, hence 2 acetyl CoA). When calculating total ATP yield, always double the per-turn values: 6 NADH, 2 FADH $_2$ , and 2 GTP from the Krebs cycle per glucose.

To memorise the order: Citrate, Isocitrate, Alpha-ketoglutarate, Succinyl CoA, Succinate, Fumarate, Malate, Oxaloacetate. Mnemonic: Can I Always See Some Funny Movie Outside.

Question

Solution — Step by Step

Why This Works

Common Mistake

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