The link reaction, also known as pyruvate oxidation or the transition reaction, is a mandatory step in aerobic cellular respiration that acts as a bridge between glycolysis and the Krebs cycle. This process converts the three-carbon product of glycolysis into the two-carbon fuel required for the next major stage of energy production when oxygen is available.
Location and Reactants
Glycolysis takes place in the cell’s cytoplasm, producing a three-carbon molecule called pyruvate. For aerobic respiration to continue, this pyruvate must be actively transported into the mitochondrial matrix, the fluid-filled space within the inner membrane. The enzymes required for the link reaction are contained within this matrix. Once inside, the three molecules required to start the reaction are pyruvate, Coenzyme A (\(\text{CoA}\)), and the electron carrier \(\text{NAD}^+\). \(\text{CoA}\) is derived from Vitamin \(\text{B}_5\) and functions as a carrier for the acetyl group, while \(\text{NAD}^+\) acts as an oxidizing agent, ready to accept high-energy electrons.
The Chemical Transformation: Pyruvate to Acetyl-CoA
The conversion of pyruvate to acetyl-CoA is catalyzed by a massive enzyme structure known as the Pyruvate Dehydrogenase Complex (\(\text{PDC}\)). This complex is a multi-enzyme system that orchestrates three distinct chemical events in quick succession. The complexity of the \(\text{PDC}\) ensures the efficient execution of this transformation.
The first chemical event is decarboxylation, where a carboxyl group is removed from the three-carbon pyruvate molecule. This lost carbon is released immediately as a molecule of carbon dioxide (\(\text{CO}_2\)), leaving behind a two-carbon fragment.
The remaining two-carbon molecule is then oxidized in the second step, meaning it loses high-energy electrons. These electrons are immediately picked up by the electron-carrying molecule \(\text{NAD}^+\), which becomes reduced to \(\text{NADH}\).
Finally, the remaining two-carbon fragment, now an acetyl group, is transferred to Coenzyme \(\text{A}\). This attachment forms the final product, Acetyl-CoA, which proceeds to the next stage of cellular respiration. The entire process is referred to as oxidative decarboxylation because it involves both the removal of a carbon atom as \(\text{CO}_2\) and the oxidation of the molecule.
The Energy Yield and Continuation of Respiration
The link reaction produces three distinct products for every molecule of pyruvate that enters the mitochondrial matrix: Acetyl-CoA, \(\text{NADH}\), and \(\text{CO}_2\). Since a single glucose molecule yields two pyruvates from glycolysis, the link reaction takes place twice for every glucose molecule processed.
The Acetyl-CoA molecule is the immediate fuel for the Krebs cycle, the next major stage of energy generation. It carries the two-carbon acetyl group into the cycle, where it will be completely broken down. The \(\text{CO}_2\) is a metabolic waste product, representing the first carbons from the original glucose molecule to be fully oxidized and released.
The \(\text{NADH}\) produced carries high-energy electrons to the final stage of aerobic respiration, the Electron Transport Chain (\(\text{ETC}\)). There, it powers the large-scale production of ATP. The link reaction itself yields no direct ATP, but it prepares the energy-rich components for the stages that follow.