The Krebs Cycle: Steps, Products and Regulation
AP Biology / first-year college · 15 flashcards · 8 quiz questions · updated 2026-08-19
The Krebs cycle — also called the citric acid cycle or the TCA cycle — is where the carbon that started as glucose finally leaves your body as carbon dioxide. It runs in the mitochondrial matrix, and its real job is not making ATP. It makes electron carriers: the NADH and FADH₂ that the electron transport chain converts into most of your ATP.
Exam questions almost always come down to three things: what goes in, what comes out per turn, and which enzyme is regulated. Everything below is organised around those.
Before the cycle: the link reaction
Glycolysis ends with pyruvate in the cytosol. The Krebs cycle starts with acetyl-CoA in the matrix, so something has to happen in between — the link reaction, carried out by the pyruvate dehydrogenase complex.
This step is not part of the cycle itself, which is exactly why it is worth marks: students count its CO₂ and NADH as cycle products and get the totals wrong.
- •Pyruvate (3C) loses one carbon as CO₂ — this is decarboxylation.
- •The remaining 2-carbon fragment is oxidised, reducing NAD⁺ to NADH.
- •Coenzyme A attaches, producing acetyl-CoA (2C).
- •Per glucose this happens twice: 2 CO₂ and 2 NADH before the cycle even begins.
The eight steps, by carbon count
Follow the carbons and the cycle stops being a list to memorise. Acetyl-CoA (2C) joins oxaloacetate (4C) to make citrate (6C). Two carbons leave as CO₂, and you are back to the 4-carbon oxaloacetate you started with.
| Step | What happens | Produced |
|---|---|---|
| 1. Citrate synthase | Acetyl-CoA (2C) + oxaloacetate (4C) → citrate (6C) | CoA released |
| 2. Aconitase | Citrate rearranges into isocitrate (6C) | — |
| 3. Isocitrate dehydrogenase | Isocitrate → α-ketoglutarate (5C) | NADH + CO₂ |
| 4. α-ketoglutarate dehydrogenase | α-ketoglutarate → succinyl-CoA (4C) | NADH + CO₂ |
| 5. Succinyl-CoA synthetase | Succinyl-CoA → succinate | GTP (or ATP) |
| 6. Succinate dehydrogenase | Succinate → fumarate | FADH₂ |
| 7. Fumarase | Fumarate + H₂O → malate | — |
| 8. Malate dehydrogenase | Malate → oxaloacetate | NADH |
What one turn produces
- •3 NADH — steps 3, 4 and 8.
- •1 FADH₂ — step 6 only.
- •1 GTP or ATP by substrate-level phosphorylation — step 5.
- •2 CO₂ — steps 3 and 4.
- •Per glucose, double everything: 6 NADH, 2 FADH₂, 2 GTP/ATP, 4 CO₂, because one glucose yields two pyruvates and therefore two turns.
Why succinate dehydrogenase is the odd one out
Seven of the eight enzymes float in the matrix. Succinate dehydrogenase is embedded in the inner mitochondrial membrane, where it doubles as Complex II of the electron transport chain.
That placement is why step 6 reduces FAD rather than NAD⁺ — and why FADH₂ ultimately yields less ATP: its electrons enter the chain after the first proton-pumping complex, so fewer protons are moved per pair of electrons.
Regulation: the cycle answers to demand
The cycle is controlled by the cell's energy state rather than by hormones. High energy shuts it down; a cell that needs ATP opens it up.
- •Isocitrate dehydrogenase (step 3) is the main control point — activated by ADP and Ca²⁺, inhibited by ATP and NADH.
- •Citrate synthase is inhibited by its own product, citrate, and by ATP and NADH.
- •α-ketoglutarate dehydrogenase is inhibited by succinyl-CoA and NADH.
- •Ca²⁺ released during muscle contraction activates the cycle, tying ATP production to the moment the muscle is actually working.
Where the cycle sits in respiration
Glycolysis (cytosol) → link reaction (matrix) → Krebs cycle (matrix) → electron transport chain and chemiosmosis (inner membrane).
Of roughly 30–32 ATP per glucose, the Krebs cycle contributes only 2 directly. Its NADH and FADH₂ account for the overwhelming majority of the rest — which is the point of the whole cycle.
Common mistakes
- ✗Counting the link reaction's CO₂ and NADH as Krebs cycle products. They come before the cycle.
- ✗Saying the cycle happens once per glucose. It happens twice — once per pyruvate.
- ✗Writing that the Krebs cycle uses oxygen. It does not directly; it stops without oxygen because the electron transport chain stops regenerating NAD⁺.
- ✗Claiming FADH₂ is produced at the same step as NADH. Only step 6 makes FADH₂.
- ✗Forgetting that oxaloacetate is regenerated, so it is a catalyst for the cycle, not a reactant consumed by it.
Flashcards
Tap a card to reveal the answer.
Where does the Krebs cycle take place?⌄
The mitochondrial matrix — except succinate dehydrogenase, which sits in the inner mitochondrial membrane.
What molecule enters the cycle?⌄
Acetyl-CoA (2 carbons), which joins oxaloacetate (4 carbons) to form citrate (6 carbons).
How many NADH per turn of the cycle?⌄
3 — from isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and malate dehydrogenase.
How many FADH₂ per turn?⌄
1, at the succinate → fumarate step.
How much ATP is made directly per turn?⌄
1 GTP (converted to ATP) by substrate-level phosphorylation at succinyl-CoA synthetase.
How many CO₂ per turn, and from which steps?⌄
2 — the isocitrate → α-ketoglutarate step and the α-ketoglutarate → succinyl-CoA step.
How many turns per glucose?⌄
Two, because glycolysis produces two pyruvates.
What is the link reaction?⌄
Pyruvate → acetyl-CoA, catalysed by pyruvate dehydrogenase: releases 1 CO₂ and makes 1 NADH per pyruvate.
Which enzyme is the main regulatory point?⌄
Isocitrate dehydrogenase — activated by ADP and Ca²⁺, inhibited by ATP and NADH.
Why is the Krebs cycle called a cycle?⌄
Oxaloacetate is consumed in step 1 and regenerated in step 8, so the pathway returns to its starting molecule.
What are the four-carbon intermediates?⌄
Succinyl-CoA, succinate, fumarate, malate and oxaloacetate.
Which step is also Complex II of the electron transport chain?⌄
Succinate dehydrogenase, the succinate → fumarate step.
Does the Krebs cycle use oxygen directly?⌄
No. It stops without oxygen only because the electron transport chain can no longer regenerate NAD⁺ and FAD.
Net products per glucose from the cycle alone?⌄
6 NADH, 2 FADH₂, 2 GTP/ATP and 4 CO₂.
What is the fate of the CO₂ produced?⌄
It diffuses out of the mitochondrion and the cell, and is exhaled — the carbons originally came from glucose.
Practice quiz
Answer first, then open the explanation.
1. How many molecules of NADH are produced in one turn of the Krebs cycle?
- A. 1
- B. 2
- C. 3
- D. 4
Show answer
C. 3
Isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and malate dehydrogenase each reduce one NAD⁺.2. Which molecule combines with acetyl-CoA in the first step?
- A. Citrate
- B. Oxaloacetate
- C. Malate
- D. Succinate
Show answer
B. Oxaloacetate
Oxaloacetate (4C) plus acetyl-CoA (2C) gives citrate (6C), catalysed by citrate synthase.3. At which step is FADH₂ produced?
- A. Isocitrate → α-ketoglutarate
- B. Succinate → fumarate
- C. Malate → oxaloacetate
- D. Citrate → isocitrate
Show answer
B. Succinate → fumarate
Succinate dehydrogenase reduces FAD, not NAD⁺, and is the only step in the cycle that does.4. How many turns of the cycle does one glucose molecule drive?
- A. One
- B. Two
- C. Four
- D. Six
Show answer
B. Two
Glycolysis splits glucose into two pyruvates, each of which becomes one acetyl-CoA — so two turns.5. Which of these happens in the link reaction rather than the cycle itself?
- A. Pyruvate is decarboxylated to acetyl-CoA
- B. Citrate is rearranged to isocitrate
- C. GTP is produced
- D. Fumarate is hydrated to malate
Show answer
A. Pyruvate is decarboxylated to acetyl-CoA
The pyruvate dehydrogenase complex performs the link reaction before the cycle begins; its CO₂ and NADH are not cycle products.6. Isocitrate dehydrogenase is inhibited by which pair?
- A. ADP and Ca²⁺
- B. ATP and NADH
- C. AMP and NAD⁺
- D. Oxygen and water
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B. ATP and NADH
High ATP and NADH signal that the cell has plenty of energy, so the cycle slows.7. Why does the Krebs cycle stop in the absence of oxygen?
- A. Oxygen is a direct reactant in step 3
- B. Acetyl-CoA cannot form without oxygen
- C. NAD⁺ and FAD are not regenerated by the electron transport chain
- D. The matrix becomes too acidic
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C. NAD⁺ and FAD are not regenerated by the electron transport chain
Without oxygen as the final electron acceptor, the carriers stay reduced and the dehydrogenase steps have nothing to reduce.8. How many carbon dioxide molecules leave per glucose from the cycle alone?
- A. 2
- B. 4
- C. 6
- D. 8
Show answer
B. 4
Two CO₂ per turn, two turns per glucose. The other two come from the link reaction.
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