The citric acid cycle - also written as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle - completes the oxidation of acetyl-CoA. All three names refer to the same 8-step cycle. Each turn burns off two carbons as CO2 and harvests electrons as NADH and FADH2 for the electron transport chain. It happens in the mitochondrial matrix.
The TCA cycle’s main job is not ATP production (it makes only 1 GTP per turn). Its main job is to strip electrons from fuel and load them onto NADH and FADH2, which then carry the electrons to the ETC where the bulk of ATP is made. Think of the TCA cycle as an electron-stripping machine, and the ETC as the actual ATP factory that runs on those electrons.
Any fuel that can be converted to acetyl-CoA enters here - glucose (via glycolysis → PDH), fatty acids (via beta-oxidation, Chapter 11), and many amino acids (Chapter 11). So the TCA cycle is the shared convergence point of essentially all catabolism.
The citric acid cycle
Pathway map
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Oxaloacetate: the gatekeeper NADH FADH₂ CO₂ released
Ways inPyruvate carboxylase tops up oxaloacetate when the cycle runs low (anaplerosis). Glutamate enters at α-ketoglutarate, and odd-chain fatty acids plus valine, isoleucine, and methionine enter at succinyl-CoA.
Ways outCitrate leaves for fatty acid and cholesterol synthesis. Malate and oxaloacetate leave for gluconeogenesis. Succinyl-CoA leaves for heme synthesis. Draining any of them slows the cycle unless OAA is replaced.
Why it needs O₂No step in the cycle uses oxygen directly, but every turn dumps NADH and FADH₂ that only the electron transport chain can re-oxidize. Without O₂, NAD⁺ runs out and the cycle stops within seconds.
The cycle is a roundabout, not a road. Acetyl-CoA joins oxaloacetate at the top, two carbons leave as CO₂ on the right, and the four-carbon skeleton is rebuilt on the way back round. The carbons that leave as CO₂ are not the two that just arrived, which is why the cycle can never make net glucose from fat.
Succinate dehydrogenase (TCA step 6) is the same protein as Complex II of the electron transport chain. It is the only TCA enzyme embedded in the inner mitochondrial membrane. Electrons from succinate oxidation go directly into CoQ (bypassing Complex I), which is why FADH2 yields less ATP than NADH (enters the ETC one step later).
What is the yield of one turn of the TCA cycle?
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Per turn (per acetyl-CoA): 3 NADH + 1 FADH2 + 1 GTP + 2 CO2. Per glucose (2 turns): 6 NADH + 2 FADH2 + 2 GTP + 4 CO2. The NADH and FADH2 carry electrons to the ETC for additional ATP production via oxidative phosphorylation.
Why does succinate dehydrogenase produce FADH2 instead of NADH like most TCA dehydrogenases?
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Succinate → fumarate is a simple alkene formation (oxidation of C-C single bond to double bond) with a smaller free energy change than the oxidation of a hydroxyl to a ketone. FAD is a better fit for lower-energy oxidations. Succinate dehydrogenase is also Complex II of the ETC - the enzyme is in the inner membrane rather than in the matrix, and FADH2 electrons feed CoQ directly.
Why does the TCA cycle not require oxygen directly yet only operates when oxygen is present?
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No TCA reaction uses O2 as a substrate. But the cycle requires NAD+ and FAD as electron acceptors. These are regenerated by the electron transport chain, which uses O2 as the final electron acceptor. Without oxygen, NAD+ and FAD remain reduced as NADH and FADH2, which would back up the cycle. So the TCA cycle is aerobic in the sense that it depends on oxygen indirectly, via the ETC.
