Short Answer
The Krebs cycle (also called the citric‑acid cycle or tricarboxylic‑acid cycle) is the central metabolic pathway that finishes the oxidation of glucose‑derived acetyl‑CoA, producing carbon dioxide and high‑energy electron carriers for the electron‑transport chain.
Where the cycle takes place
All eight reactions occur in the matrix of the mitochondrion, the inner compartment of the organelle that houses the enzymes of aerobic respiration.
Overall inputs and outputs (per turn)
- Input: 1 acetyl‑CoA (2 C), 3 NAD⁺, 1 FAD, 1 ADP + Pᵢ, 2 H₂O
- Output: 2 CO₂, 3 NADH, 1 FADH₂, 1 GTP (≈ATP)
Because each glucose yields two molecules of pyruvate → two acetyl‑CoA, the cycle runs twice per glucose, doubling the numbers above.
Step‑by‑step sequence
- Condensation – Acetyl‑CoA (2 C) combines with oxaloacetate (4 C) to form citrate (6 C). Enzyme: citrate synthase.
- Isomerization – Citrate is rearranged to isocitrate by aconitase.
- First oxidative decarboxylation – Isocitrate is oxidized, reducing NAD⁺ to NADH and releasing one CO₂, producing α‑ketoglutarate (5 C). Enzyme: isocitrate dehydrogenase.
- Second oxidative decarboxylation – α‑Ketoglutarate is oxidized, reducing another NAD⁺ to NADH and releasing a second CO₂, yielding succinyl‑CoA (4 C). Enzyme: α‑ketoglutarate dehydrogenase complex.
- Substrate‑level phosphorylation – Succinyl‑CoA is converted to succinate, driving synthesis of GTP (or ATP) from ADP and Pᵢ. Enzyme: succinyl‑CoA synthetase.
- Oxidation of succinate – Succinate is oxidized to fumarate, reducing FAD to FADH₂. Enzyme: succinate dehydrogenase (also Complex II of the ETC).
- Hydration – Fumarate is hydrated to malate by fumarase.
- Final oxidation – Malate is oxidized to oxaloacetate, reducing NAD⁺ to NADH and completing the loop. Enzyme: malate dehydrogenase.
Why each step matters
Each oxidation transfers two electrons to an electron carrier (NAD⁺ or FAD), storing energy that will later be used by the electron‑transport chain to make ~2.5 ATP per NADH and ~1.5 ATP per FADH₂. The GTP produced is a direct “high‑energy phosphate” that can be used immediately for cellular work.
Worked example: Energy yield from one glucose
One glucose → 2 pyruvate → 2 acetyl‑CoA → two turns of the cycle.
| Product | Per turn | Per glucose (2 turns) |
|---|---|---|
| NADH | 3 | 6 |
| FADH₂ | 1 | 2 |
| GTP (ATP) | 1 | 2 |
| CO₂ | 2 | 4 |
When these carriers enter the electron‑transport chain they can generate roughly 2.5 ATP per NADH and 1.5 ATP per FADH₂, giving about 15 ATP from NADH, 3 ATP from FADH₂, plus the 2 ATP (GTP) made directly – ~20 ATP contributed by the Krebs cycle alone. Combined with glycolysis and oxidative phosphorylation, the total rises to ~30–32 ATP per glucose, as illustrated in many textbooks.
Self‑check question
Question: Which enzyme in the cycle directly links the Krebs cycle to the electron‑transport chain?
Answer: Succinate dehydrogenase, because it reduces FAD to FADH₂ and is also Complex II of the ETC.
Next step in cellular respiration
After the Krebs cycle, the high‑energy carriers (NADH, FADH₂) feed into the electron‑transport chain, where oxidative phosphorylation produces the bulk of cellular ATP.
FAQ
What is the primary purpose of the Krebs cycle?
The Krebs cycle completes the oxidation of acetyl‑CoA derived from glucose, producing carbon dioxide, NADH, FADH₂, and GTP/ATP, which supply the high‑energy electrons and phosphate bonds needed for oxidative phosphorylation.
Where does the Krebs cycle take place within the cell?
All eight reactions of the Krebs cycle occur in the matrix of the mitochondrion, the inner compartment of the organelle that houses the enzymes of aerobic respiration.
How many ATP equivalents are generated from one molecule of glucose by the Krebs cycle alone?
Each turn of the cycle yields 3 NADH, 1 FADH₂, and 1 GTP. Because one glucose provides two acetyl‑CoA, the cycle runs twice, producing a total of 6 NADH, 2 FADH₂, and 2 GTP. When these carriers feed the electron‑transport chain (≈2.5 ATP per NADH and ≈1.5 ATP per FADH₂), the Krebs cycle contributes roughly 20 ATP equivalents per glucose.
Which enzyme directly links the Krebs cycle to the electron‑transport chain?
Succinate dehydrogenase links the cycle to the electron‑transport chain because it reduces FAD to FADH₂ and is also known as Complex II of the ETC.
What are the main inputs and outputs of one turn of the Krebs cycle?
Inputs per turn: 1 acetyl‑CoA, 3 NAD⁺, 1 FAD, 1 ADP + Pᵢ, and 2 H₂O. Outputs per turn: 2 CO₂, 3 NADH, 1 FADH₂, and 1 GTP (≈ATP).
How does the Krebs cycle connect to glycolysis and oxidative phosphorylation?
Glycolysis converts glucose to pyruvate, which is decarboxylated to acetyl‑CoA that enters the Krebs cycle. The NADH and FADH₂ produced by the cycle donate electrons to the electron‑transport chain, driving oxidative phosphorylation and the bulk of ATP synthesis.
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