You are about to meet one of the most elegant cycles in biochemistry. The Krebs cycle (also called the citric acid cycle or TCA cycle) is the central hub of cellular respiration — the place where the final breakdown of carbohydrates, fats, and proteins converges.
The intuition: Why a cycle?
Imagine you are running a factory that needs to burn fuel completely. The fuel arrives in small, manageable packets called acetyl-CoA (each packet is a 2-carbon molecule). But you cannot just set fire to a 2-carbon molecule in one step — that would be inefficient and dangerous. Instead, you need a molecular assembly line that systematically strips away carbon atoms, one at a time, and captures the energy released.
The cycle is a closed loop of chemical reactions. Think of it as a circular conveyor belt. A 4-carbon molecule (oxaloacetate) sits at the start of the belt. The 2-carbon acetyl-CoA joins it, making a 6-carbon molecule (citrate). Then, through a series of steps, the belt rotates, and two carbons are removed as CO₂. At the end of one full rotation, the original 4-carbon molecule is regenerated, ready to accept another acetyl-CoA. The belt never stops — it just keeps turning.
Why a cycle? Because the starting molecule is reused. You do not need to build a new one each time. This makes the process continuous and efficient.
The precise statement
The Krebs cycle is a sequence of eight enzyme-catalysed reactions that occur in the mitochondrial matrix. Its overall job is to completely oxidise the acetyl group (2 carbons) of acetyl-CoA to two molecules of CO₂, while capturing the released energy in the form of reduced coenzymes (NADH and FADH₂) and one molecule of GTP (which is easily converted to ATP).
Here is the net equation for one turn of the cycle:
Acetyl-CoA+3NAD++FAD+GDP+Pi+2H2O→2CO2+3NADH+FADH2+GTP+CoA+3H+
The eight steps in plain language
- Condensation: Acetyl-CoA (2C) joins oxaloacetate (4C) to form citrate (6C). The CoA is released.
- Isomerisation: Citrate is rearranged into isocitrate (still 6C).
- First oxidation & decarboxylation: Isocitrate loses one CO₂ and gives one NADH, forming α-ketoglutarate (5C).
- Second oxidation & decarboxylation: α-ketoglutarate loses another CO₂ and gives one NADH, forming succinyl-CoA (4C).
- Substrate-level phosphorylation: Succinyl-CoA is converted to succinate (4C), producing GTP (or ATP in some organisms).
- Third oxidation: Succinate is oxidised to fumarate (4C), producing FADH₂.
- Hydration: Fumarate adds water to become malate (4C).
- Fourth oxidation: Malate is oxidised to oxaloacetate (4C), producing another NADH. The cycle is now ready to start again.
A mnemonic to remember the order: Can I Keep Selling Sex For Money, Officer? — Citrate, Isocitrate, α-Ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate.
What is the point of all this? …