Step by Step
Loc
Location — mitochondrial matrix
The Krebs cycle (citric acid cycle / TCA cycle) occurs in the mitochondrial matrix. Acetyl-CoA (2C) combines with oxaloacetate (4C) → citrate (6C). The cycle regenerates oxaloacetate at the end, allowing it to run continuously.
Memory trick: TCA = 'Totally Circular Affair' — it goes around and around.
Ent
Entry point — acetyl-CoA
Acetyl-CoA is the entry molecule for the Krebs cycle. It comes from: pyruvate (via pyruvate dehydrogenase), fatty acid beta-oxidation, and amino acid catabolism. Per glucose: 2 pyruvate → 2 acetyl-CoA → 2 turns of the Krebs cycle.
Per
Per turn yields
Each turn of the cycle produces: 3 NADH, 1 FADH₂, 1 GTP (or ATP), 2 CO₂ released. Per glucose (2 turns): 6 NADH + 2 FADH₂ + 2 GTP. NADH and FADH₂ carry electrons to the ETC for ATP synthesis.
Memory trick: 3-1-1-2. Three NADH, One FADH₂, One GTP, Two CO₂.
Reg
Key regulatory enzymes
Rate-limiting step: isocitrate dehydrogenase (step 3). Also regulated: citrate synthase (step 1), α-ketoglutarate dehydrogenase (step 4). All three are inhibited by high NADH and ATP (energy surplus) and activated by ADP and NAD⁺ (energy needed).
Applied Walkthrough
1
Pyruvate enters the mitochondria and is converted to acetyl-CoA by pyruvate dehydrogenase (releasing CO₂ and producing NADH).
2
Acetyl-CoA (2C) joins oxaloacetate (4C) → citrate (6C). The cycle begins.
3
Over 8 steps, 2 carbons are released as CO₂, electrons are transferred to NAD⁺ and FAD, and GTP is produced by substrate-level phosphorylation.
4
Oxaloacetate is regenerated — ready for the next acetyl-CoA. Per glucose: 2 full turns = 6 NADH + 2 FADH₂ + 2 GTP (plus 4 CO₂ released).
Exam Application
Exams test the location (mitochondrial matrix), what enters (acetyl-CoA + oxaloacetate), per-turn yields (3 NADH + 1 FADH₂ + 1 GTP + 2 CO₂), and the total per glucose (multiply by 2). The rate-limiting enzyme (isocitrate dehydrogenase) and the three sources of acetyl-CoA are also high yield.
⚠ Common Trap
Students confuse per-turn yields with per-glucose yields — remember the cycle runs TWICE per glucose (once per pyruvate). Also: the Krebs cycle does NOT directly produce much ATP — its main role is generating NADH and FADH₂ for the ETC. The 2 CO₂ released per turn are why we exhale CO₂.
✓ Quick Self-Check
1. Where does the Krebs cycle occur?
In the mitochondrial matrix.
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2. What molecule enters the Krebs cycle?
Acetyl-CoA (2C) — it combines with oxaloacetate (4C) to form citrate (6C).
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3. What does each turn of the Krebs cycle produce?
3 NADH + 1 FADH₂ + 1 GTP + 2 CO₂.
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4. How many turns does the Krebs cycle make per glucose?
2 turns — one for each pyruvate (each glucose produces 2 pyruvates).
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5. What is the rate-limiting enzyme of the Krebs cycle?
Isocitrate dehydrogenase (step 3).
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