The Link Reaction Connects Glycolysis to the Krebs CycleGlycolysis in the cytoplasm breaks glucose down into pyruvate (3C).The Krebs cycle in the mitochondrial matrix needs acetyl groups (2C).There is a carbon mismatch, because pyruvate has 3 carbons but the Krebs cycle uses 2-carbon acetyl groups.The link reaction bridges this gap in the mitochondrial matrix by converting pyruvate (3C) into a 2-carbon acetyl group.The acetyl group then joins coenzyme A to form acetyl-CoA.AnalogyThe link reaction is a bridge between two locations: glycolysis in the cytoplasm and the Krebs cycle in the mitochondrial matrix.Without this bridge, the energy stored in pyruvate could not reach the Krebs cycle.How the Link Reaction Works Step by StepPyruvate oxidationStep 1: Decarboxylation (removing carbon)One carbon atom is removed from pyruvate (3C) as carbon dioxide (CO₂).This leaves a 2-carbon molecule.Step 2: Oxidation (removing hydrogen)Hydrogen is removed from the 2-carbon molecule.This hydrogen is accepted by NAD to form reduced NAD (NADH).Step 3: Acetyl group joins coenzyme AThe remaining 2-carbon acetyl group joins coenzyme A (CoA) to form acetyl-CoA.Coenzyme A carries the acetyl group into the Krebs cycle.TipThe link reaction occurs twice per glucose, because each glucose yields two pyruvate molecules.Lipids Also Feed Acetyl Groups Into the CycleCarbohydrates reach acetyl-CoA through glycolysis, then pyruvate, then the link reaction.Fatty acids form acetyl-CoA directly through beta-oxidation, bypassing glycolysis and the link reaction.Both pathways converge at acetyl-CoA, which enters the Krebs cycle.NoteWhether the fuel is carbohydrate or lipid, the Krebs cycle always processes 2-carbon acetyl groups carried by coenzyme A.The full comparison of lipid and carbohydrate fuels is covered in C1.2.17.Active recallWhere in the cell does the link reaction occur?Which molecule accepts the hydrogen removed during the oxidation step?What is the role of coenzyme A in the link reaction?How many times does the link reaction occur per glucose molecule?How do fatty acids form acetyl-CoA?