Question
Draw the Krebs cycle (citric acid cycle / TCA cycle) and explain each step with the enzymes involved. Mention the substrates, products, and energy carriers generated at each step.
(NEET, CBSE Class 11 — Respiration in Organisms)
Solution — Step by Step
The cycle begins when acetyl CoA (2C) combines with oxaloacetate (OAA) (4C) to form citrate (6C). The enzyme is citrate synthase. CoA is released in this step.
This is the only step where a 2-carbon unit enters the cycle — everything else is rearrangement and oxidation.
Citrate (6C) is converted to isocitrate (6C) by the enzyme aconitase. This is an isomerisation — the hydroxyl group shifts position. No carbon is lost here.
Isocitrate dehydrogenase oxidises isocitrate to alpha-ketoglutarate (5C). One CO is released, and one NADH is produced. This is the first decarboxylation and the rate-limiting step of the cycle.
Alpha-ketoglutarate dehydrogenase converts alpha-ketoglutarate (5C) to succinyl CoA (4C). Another CO is released and one NADH is produced. This enzyme complex is structurally similar to pyruvate dehydrogenase.
Succinyl CoA synthetase (or succinate thiokinase) converts succinyl CoA to succinate (4C). The energy from the thioester bond is used to produce 1 GTP (equivalent to 1 ATP). This is the only substrate-level phosphorylation in the Krebs cycle.
graph TD
A["Acetyl CoA (2C) + OAA (4C)"] -->|Citrate synthase| B["Citrate (6C)"]
B -->|Aconitase| C["Isocitrate (6C)"]
C -->|"Isocitrate dehydrogenase<br/>NADH + CO₂"| D["α-Ketoglutarate (5C)"]
D -->|"α-KG dehydrogenase<br/>NADH + CO₂"| E["Succinyl CoA (4C)"]
E -->|"Succinyl CoA synthetase<br/>GTP"| F["Succinate (4C)"]
F -->|"Succinate dehydrogenase<br/>FADH₂"| G["Fumarate (4C)"]
G -->|Fumarase| H["Malate (4C)"]
H -->|"Malate dehydrogenase<br/>NADH"| I["Oxaloacetate (4C)"]
I --> ASuccinate dehydrogenase oxidises succinate to fumarate (4C), producing 1 FADH. This is the only enzyme in the cycle that is embedded in the inner mitochondrial membrane (it is also Complex II of the ETC).
Fumarase hydrates fumarate to form malate (4C). Water is added across the double bond. No energy carriers are produced.
Malate dehydrogenase oxidises malate to regenerate oxaloacetate (4C), producing 1 NADH. OAA is now ready to accept another acetyl CoA, and the cycle continues.
Why This Works
The Krebs cycle is essentially a molecular machine for extracting energy from the 2-carbon acetyl group. The two carbons that enter as acetyl CoA leave as 2 CO molecules (steps 3 and 4). The energy is captured as reduced coenzymes — 3 NADH, 1 FADH, and 1 GTP per turn.
The reason it is a cycle (rather than a linear pathway) is efficiency. Oxaloacetate is regenerated at the end, so only a catalytic amount is needed. The cycle can run continuously as long as acetyl CoA keeps arriving.
Per molecule of glucose, the Krebs cycle runs twice (because one glucose gives 2 pyruvate, which give 2 acetyl CoA). So the total yield per glucose from the Krebs cycle is: 6 NADH, 2 FADH, 2 GTP.
Alternative Method — Tracking Carbon Numbers
A useful way to remember the cycle: track the number of carbon atoms.
4C (OAA) + 2C (Acetyl CoA) = 6C (Citrate). Then 6C loses one CO to give 5C, and 5C loses another CO to give 4C. The remaining steps convert 4C back to OAA (4C) through oxidation and hydration. Two carbons in, two carbons out as CO.
Mnemonic for the intermediates: Can I Always See Some Funny Monkeys Outside — Citrate, Isocitrate, Alpha-ketoglutarate, Succinyl CoA, Succinate, Fumarate, Malate, Oxaloacetate.
Common Mistake
Students often confuse the location: the Krebs cycle occurs in the mitochondrial matrix, not in the cytoplasm or on the inner membrane. Only succinate dehydrogenase (step 6) is membrane-bound. All other enzymes are soluble in the matrix.
Another frequent error: saying the Krebs cycle produces ATP directly. It does not — it produces GTP (1 per turn). The bulk of ATP comes later when NADH and FADH donate electrons to the electron transport chain.