Metabolism
The Krebs cycle explained
Also called the citric acid cycle or TCA cycle, this is the metabolic hub where carbohydrate, fat, and protein breakdown all converge.
Where it happens and what enters
The cycle runs in the mitochondrial matrix. Its input is acetyl-CoA — a 2-carbon unit produced from pyruvate (via pyruvate dehydrogenase), from fatty acids (via beta-oxidation), and from certain amino acids.
Yield per turn
3 NADH · 1 FADH2 · 1 GTP (or ATP) · 2 CO2
One glucose produces two acetyl-CoA, so it drives two turns: 6 NADH, 2 FADH2, 2 GTP.
The cycle in brief
| Step | Conversion | Produces |
|---|---|---|
| 1 | Acetyl-CoA + oxaloacetate → citrate | — |
| 2 | Citrate → isocitrate | — |
| 3 | Isocitrate → α-ketoglutarate | NADH, CO2 |
| 4 | α-ketoglutarate → succinyl-CoA | NADH, CO2 |
| 5 | Succinyl-CoA → succinate | GTP |
| 6 | Succinate → fumarate | FADH2 |
| 7 | Fumarate → malate | — |
| 8 | Malate → oxaloacetate | NADH |
What the cycle is actually for
A frequent misconception is that the Krebs cycle "makes ATP." It makes very little directly — just one GTP per turn. Its real function is to strip electrons from fuel molecules and load them onto the carriers NADH and FADH2, which then deliver them to the electron transport chain, where the great majority of ATP is actually generated.
Regulation
- Citrate synthase — inhibited by ATP, NADH, and succinyl-CoA
- Isocitrate dehydrogenase — the main control point; activated by ADP, inhibited by ATP and NADH
- α-ketoglutarate dehydrogenase — inhibited by its products and by NADH
The pattern is consistent across all three: high energy charge slows the cycle, low energy charge accelerates it.
Frequently asked questions
What does one turn of the Krebs cycle produce?
One turn produces 3 NADH, 1 FADH2, 1 GTP (or ATP), and 2 CO2. Because each glucose molecule yields two acetyl-CoA, one glucose drives two turns of the cycle.
Where does the Krebs cycle take place?
In the mitochondrial matrix. This is distinct from glycolysis, which occurs in the cytosol, and from the electron transport chain, which is embedded in the inner mitochondrial membrane.
Why does the Krebs cycle make so little ATP directly?
Its purpose is to strip electrons from fuel molecules onto NADH and FADH2 rather than to make ATP itself. Those carriers then feed the electron transport chain, where most ATP is generated.
Keep reading: Glycolysis explained · The electron transport chain · Beta-oxidation explained