Link Reaction and Krebs Cycle

If glucose has been converted to pyruvate by glycolysis in the cytoplasm, the next stage is to transport the pyruvate into the mitochondrial matrix and oxidise it fully to CO₂. This happens in two linked pathways: the link reaction (pyruvate → acetyl CoA) and the Krebs cycle (also called the citric acid cycle or TCA cycle). OCR specification module 5.2.2(d) requires detailed knowledge of both. Together they release most of the CO₂ from aerobic respiration and produce the reduced NAD and reduced FAD that drive the bulk of ATP production in the next stage.

Key Definitions:

• Link reaction — the reaction that "links" glycolysis to the Krebs cycle by converting pyruvate to acetyl CoA.
• Acetyl CoA — a 2-carbon acetyl group bound to coenzyme A; the substrate that enters the Krebs cycle.
• Krebs cycle — a cyclic series of reactions in the mitochondrial matrix that completely oxidises the acetyl group from acetyl CoA, producing CO₂, reduced NAD, reduced FAD and ATP.
• Decarboxylation — removal of a carboxyl group as CO₂.
• Dehydrogenation — removal of hydrogen (with electrons) to a coenzyme (NAD or FAD).

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The Link Reaction

After glycolysis, pyruvate is actively transported into the mitochondrial matrix. Here, each pyruvate (3C) undergoes three steps:

flowchart LR
    PYR[Pyruvate - 3C] -->|Decarboxylation| C2[2C fragment + CO2]
    C2 -->|Dehydrogenation| NAD[Reduced NAD]
    C2 -->|CoA added| ACo[Acetyl CoA - 2C]

Step-by-step

1. Decarboxylation: pyruvate loses a CO₂ molecule. This leaves a 2-carbon acetyl group.
2. Dehydrogenation: the acetyl group is oxidised — a pair of hydrogens (with electrons) is removed and transferred to NAD, forming reduced NAD.
3. Addition of coenzyme A: the acetyl group is attached to coenzyme A, forming acetyl CoA.

Products Per Pyruvate

• 1 CO₂ (released as waste)
• 1 reduced NAD
• 1 acetyl CoA

Per Glucose (since each glucose produces 2 pyruvates)

• 2 CO₂
• 2 reduced NAD
• 2 acetyl CoA

No ATP is made directly in the link reaction — it is purely a preparation step.

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The Krebs Cycle

The Krebs cycle (named after Hans Krebs, who worked it out in 1937) takes the acetyl group from acetyl CoA and oxidises it completely to CO₂. It is called a "cycle" because the starting molecule is regenerated at the end, allowing it to accept another acetyl group.

flowchart TB
    ACo[Acetyl CoA - 2C] -->|+ Oxaloacetate 4C| CIT[Citrate - 6C]
    CIT -->|Decarboxylation + NAD reduced| C5[5C compound]
    C5 -->|Decarboxylation + NAD reduced + ATP made| C4a[4C compound]
    C4a -->|FAD reduced| C4b[4C intermediate]
    C4b -->|NAD reduced| OAA[Oxaloacetate - 4C]
    OAA --> CIT
    CIT -. 2 CO2 out .-> OUT1[CO2]
    C5 -. CO2 out .-> OUT1

Step-by-step (Per Turn = Per Acetyl CoA)

1. Condensation: acetyl CoA (2C) combines with oxaloacetate (4C) to form citrate (6C). Coenzyme A is released and recycled.
2. First decarboxylation and dehydrogenation: citrate is converted to a 5-carbon compound, releasing 1 CO₂ and reducing 1 NAD → 1 reduced NAD.
3. Second decarboxylation and dehydrogenation: the 5C compound is converted to a 4-carbon compound, releasing 1 more CO₂ and reducing another NAD → 1 reduced NAD. At the same time, 1 ATP is made by substrate-level phosphorylation.
4. Third dehydrogenation: a FAD molecule is reduced → 1 reduced FAD.
5. Fourth dehydrogenation: another NAD is reduced → 1 reduced NAD, regenerating oxaloacetate ready to accept another acetyl CoA.

Products Per Turn of the Krebs Cycle

Product	Amount
CO₂	2
Reduced NAD	3
Reduced FAD	1
ATP	1

Per Glucose (2 turns, because 2 acetyl CoAs from one glucose)

Product	Amount
CO₂	4
Reduced NAD	6
Reduced FAD	2
ATP	2

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Cumulative Tally So Far (Per Glucose)

Stage	ATP	Reduced NAD	Reduced FAD	CO₂
Glycolysis	2 (net)	2	0	0
Link reaction	0	2	0	2
Krebs cycle	2	6	2	4
Total	4	10	2	6

Six CO₂ is the total from one glucose — exactly what the summary equation predicts. The bulk of the energy, however, is now locked up in reduced NAD and reduced FAD, not in ATP directly. These reduced coenzymes will release their stored energy in the next stage: oxidative phosphorylation.

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Where Do The Carbons Go?