The Krebs cycle

The Krebs cycle is the stage of aerobic respiration that follows the link reaction. For A-level Biology you need to know that it happens in the mitochondrial matrix, and that acetyl coenzyme A (2C) joins a four-carbon molecule (oxaloacetate) to make a six-carbon molecule (citrate). A series of oxidation-reduction reactions then turns this back into oxaloacetate, releasing carbon dioxide and making reduced NAD, reduced FAD and ATP.

Where the Krebs cycle fits in respiration

The Krebs cycle needs a supply of acetyl coenzyme A from the link reaction, and it hands its reduced coenzymes on to oxidative phosphorylation. It is also called the citric acid cycle or the tricarboxylic acid (TCA) cycle.

Krebs cycle diagram

Krebs cycle steps

1. Acetyl CoA joins oxaloacetate. The two-carbon acetyl group from acetyl coenzyme A combines with oxaloacetate (4C) to form citrate (6C). Coenzyme A is released and goes back to the link reaction to collect another acetyl group.
2. Citrate becomes a 5C compound. Citrate is decarboxylated (one CO₂ is removed) and dehydrogenated (hydrogen is removed). The hydrogen reduces NAD to reduced NAD.
3. The 5C compound becomes a 4C compound. Another decarboxylation and dehydrogenation release a second CO₂ and make another reduced NAD. One ATP is made directly, by substrate-level phosphorylation.
4. The 4C compound is turned back into oxaloacetate. More dehydrogenation reactions make one reduced FAD and one more reduced NAD, and regenerate oxaloacetate, ready to accept the next acetyl group.

Because oxaloacetate is remade at the end, the reactions form a cycle: it keeps turning as long as acetyl CoA, NAD and FAD are supplied.

Products of the Krebs cycle

One glucose gives two pyruvates, and each pyruvate gives one acetyl CoA in the link reaction, so the Krebs cycle turns twice for every glucose molecule.

Check your understanding.

What happens to the products

• Carbon dioxide diffuses out of the mitochondrion and the cell, and is a waste product.
• Reduced NAD and reduced FAD carry hydrogen (protons and electrons) to the electron transfer chain on the inner mitochondrial membrane. There they are used to make most of the cell's ATP by oxidative phosphorylation, and are oxidised back to NAD and FAD for reuse.
• ATP made directly is available for the cell's energy needs.
• Oxaloacetate is regenerated, so the cycle can continue.

If there is no oxygen, the electron transfer chain stops, NAD and FAD aren't regenerated, and the Krebs cycle stops too. So, although it doesn't use oxygen directly, the Krebs cycle only runs in aerobic respiration.

Worked examples

Example 1: counting carbon atoms

Glucose has 6 carbon atoms. In the link reaction, 2 leave as CO₂ (one from each pyruvate), leaving two acetyl groups with 2 carbons each. In the Krebs cycle, each turn releases 2 CO₂, so the 4 remaining carbons all leave as CO₂. In total, all 6 carbons of glucose end up in 6 CO₂, matching the respiration equation C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O.

Example 2: reduced NAD from one glucose

How many reduced NAD molecules are made from one glucose by the end of the Krebs cycle? Glycolysis makes 2, the link reaction makes 2 and the Krebs cycle makes 6, so the total is 10, plus 2 reduced FAD from the Krebs cycle.

Example 3: an exam-style explanation

Explain why the Krebs cycle is described as a series of oxidation-reduction reactions. Hydrogen is removed from the intermediate compounds (they are oxidised, or dehydrogenated) and accepted by NAD and FAD, which are reduced.

Common mistakes

• Putting the Krebs cycle in the cytoplasm. It is in the mitochondrial matrix.
• Forgetting to double for glucose. Two turns per glucose: 4 CO₂, 6 reduced NAD, 2 reduced FAD, 2 ATP.
• Saying the Krebs cycle makes most of the ATP. Most ATP comes from oxidative phosphorylation.
• Saying oxygen is used in the Krebs cycle. Oxygen is only needed later, as the final electron acceptor.
• Mixing up the carbon numbers. 2C acetyl + 4C oxaloacetate = 6C citrate.
• Missing substrate-level phosphorylation. The ATP made in the Krebs cycle is made directly, not by the electron transfer chain.

Practice questions

1. Where in the cell does the Krebs cycle take place?
2. Name the six-carbon molecule formed at the start of the cycle.
3. How many molecules of reduced FAD are made from two molecules of glucose?
4. Explain why the Krebs cycle stops if oxygen is not available.

Answers: 1) The mitochondrial matrix. 2) Citrate. 3) Each glucose gives 2, so 4. 4) Without oxygen the electron transfer chain stops, so reduced NAD and reduced FAD can't be oxidised back to NAD and FAD, and the Krebs cycle runs out of them.

Practise with a short timed paper

Respiration in detail is in the second year of A-level Biology. The daily A-level Biology: Year 2 paper is a short timed paper of 8 questions, with a new one every day. For the whole of respiration, see the cellular respiration guide, and for where it all happens, the mitochondria guide.

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