The Link Reaction Connects Glycolysis to the Krebs Cycle
- Glycolysis (in the cytoplasm) breaks down glucose into pyruvate (3C).
- The Krebs cycle (in the mitochondrial matrix) processes acetyl groups (2C).
- There's a mismatch: pyruvate has 3 carbons, but the Krebs cycle needs 2-carbon acetyl groups.
- The link reaction bridges this gap by converting pyruvate (3C) into a 2-carbon acetyl group by removing one carbon and some hydrogens.
- The acetyl group is then attached to coenzyme A, forming acetyl-CoA.
- Think of the link reaction as a bridge connecting two cities: glycolysis in the cytoplasm and the Krebs cycle in the mitochondrial matrix.
- Without this bridge, energy flow would be interrupted.
Acetyl-CoA eventually carries the acetyl group into the Krebs cycle (more in C1.2.14)
Step-by-Step: How the Link Reaction Works
- Step 1: Decarboxylation (Removing Carbon)
- One carbon atom is removed from pyruvate (3C) as carbon dioxide (CO₂).
- This reduces pyruvate from 3 carbons to 2 carbons.
- Step 2: Oxidation (Removing Hydrogen)
- Hydrogen atoms are removed from the 2-carbon molecule.
- These hydrogens (with their electrons) are transferred to NAD⁺, reducing it to NADH.
- Step 3: Acetyl Group Attached to Coenzyme A
- The remaining 2-carbon acetyl group is attached to coenzyme A (CoA).
- This forms acetyl-CoA.
- Coenzyme A acts as a carrier, transporting the acetyl group to the Krebs cycle.
The Link Reaction occurs twice per glucose molecule, since each glucose molecule produces two pyruvate molecules.
Both Carbohydrates and Lipids Produce Acetyl Groups
- Carbohydrates are broken down through glycolysis → pyruvate → link reaction → acetyl-CoA.
- Lipids (fatty acids) are broken down through beta-oxidation directly into acetyl-CoA, bypassing glycolysis and the link reaction.
- Both pathways converge at acetyl-CoA, which enters the Krebs cycle.
Regardless of whether the original substrate is carbohydrate or lipid, the Krebs cycle always processes 2-carbon acetyl groups carried by coenzyme A.
Self review- Where does the link reaction occur?
- What molecule accepts the hydrogens removed during oxidation?
- What is the role of coenzyme A?
- How many times does the link reaction occur per glucose molecule?
- How do lipids enter the pathway that leads to the Krebs cycle?
- Why is the link reaction called a "link"?



