The link reaction explained for A-Level Biology

The link reaction is the stage of aerobic respiration that connects glycolysis to the Krebs cycle. It happens inside the mitochondrial matrix, and its job is to convert each pyruvate molecule from glycolysis into a 2-carbon acetyl group joined to coenzyme A. In plain terms: Pyruvate enters the mitochondrion, loses a carbon dioxide molecule, gets oxidised, and ends up as acetyl CoA ready to feed the Krebs cycle.

This guide explains what the link reaction is, why it matters, the exact products from one molecule of glucose, and the mark-scheme wording AQA examiners want to see in a 4-mark question.

Aerobic respiration has four stages: Glycolysis, the link reaction, the Krebs cycle, and oxidative phosphorylation. Glycolysis happens in the cytoplasm and produces two pyruvate molecules per glucose. The link reaction is the bridge between glycolysis and the Krebs cycle.

Pyruvate cannot enter the Krebs cycle directly. It first has to be converted into acetyl CoA, and that conversion is exactly what the link reaction does. Without it, the carbon from glucose would never reach the Krebs cycle, and oxidative phosphorylation would have no reduced coenzymes to use.

The link reaction takes pyruvate (a 3-carbon molecule) and turns it into acetyl coenzyme A (a 2-carbon acetyl group attached to coenzyme A). Three things happen to each pyruvate molecule in a single coordinated step catalysed by the pyruvate dehydrogenase complex.

First, pyruvate is decarboxylated. One carbon is removed as carbon dioxide. Second, pyruvate is dehydrogenated. Hydrogen is removed and picked up by NAD to form reduced NAD (NADH). Third, the remaining 2-carbon acetyl group is attached to coenzyme A to form acetyl CoA.

Glycolysis splits one glucose into two pyruvates. That means the link reaction happens twice per glucose molecule. AQA loves asking students to scale the products from one pyruvate up to one glucose, and this is where careless answers lose marks.

Per pyruvate the link reaction produces one acetyl CoA, one carbon dioxide, and one reduced NAD. Per glucose, double everything: Two acetyl CoA, two carbon dioxide, and two reduced NAD.

The link reaction itself does not produce any ATP. That sometimes surprises students who expect every respiration stage to generate ATP. The role of the link reaction is to set up later stages by producing acetyl CoA and reduced NAD.

The reduced NAD that comes out of the link reaction is the real prize. It carries hydrogen to the electron transport chain in oxidative phosphorylation, where each reduced NAD ends up generating around 2.5 ATP. So the link reaction contributes to ATP yield indirectly, through the reduced NAD it produces.

Coenzyme A is a small organic molecule that acts as a carrier for the 2-carbon acetyl group. It picks the acetyl group up after the link reaction and hands it off to the Krebs cycle, where the acetyl group joins oxaloacetate to form citrate.

A-Level mark schemes accept the term coenzyme A or its abbreviation CoA. You do not need to draw its structure, but you should know it is a carrier molecule and that it is reused after delivering its acetyl group.

Question: Describe what happens in the link reaction. (4 marks)

Model answer: Pyruvate enters the mitochondrial matrix from the cytoplasm. It is decarboxylated, releasing one molecule of carbon dioxide. It is also dehydrogenated, with the hydrogen accepted by NAD to form reduced NAD. The remaining 2-carbon acetyl group combines with coenzyme A to form acetyl CoA.

Notice the answer does not waste time on glycolysis or the Krebs cycle. It stays on the link reaction itself and ticks off the four mark-scheme points cleanly.

Acetyl CoA enters the Krebs cycle by combining with a 4-carbon molecule called oxaloacetate to form a 6-carbon molecule called citrate. Coenzyme A is released and can be reused in the next link reaction.

The Krebs cycle then strips carbons and hydrogens from citrate over several steps, producing more carbon dioxide, more reduced NAD, reduced FAD, and a small amount of ATP. Every reduced coenzyme produced here, and in the link reaction, ends up driving oxidative phosphorylation.