describe the link reaction, including the role of coenzyme A in the transfer of acetyl (2C) groups

Published by Patrick Mutisya · 14 days ago

Cambridge A‑Level Biology 9700 – Respiration: The Link Reaction

Respiration – Overview

Cellular respiration consists of three major stages that convert the energy stored in glucose into usable ATP:

  1. Glycolysis (cytoplasm)

  2. Link reaction – also called pyruvate decarboxylation (mitochondrial matrix)

  3. The citric acid (Krebs) cycle and oxidative phosphorylation (mitochondrial matrix and inner membrane)

Link Reaction (Pyruvate Decarboxylation)

Location

The link reaction occurs in the matrix of the mitochondrion, immediately after glycolysis transports pyruvate into the organelle.

Overall Chemical Equation

For each molecule of pyruvate:

\$\text{Pyruvate} + \text{CoA‑SH} + \text{NAD}^+ \;\longrightarrow\; \text{Acetyl‑CoA} + \text{CO}_2 + \text{NADH} + \text{H}^+\$

Key Enzyme

The reaction is catalysed by the multienzyme complex pyruvate dehydrogenase complex (PDC). The complex contains three core enzymes:

  • Pyruvate dehydrogenase (E1) – decarboxylates pyruvate.

  • Dihydrolipoamide transacetylase (E2) – transfers the acetyl group to CoA.

  • Dihydrolipoamide dehydrogenase (E3) – regenerates the oxidised form of lipoamide and produces NADH.

Step‑by‑Step Mechanism

  1. Decarboxylation of pyruvate (E1): Pyruvate (3‑C) loses one carbon as CO₂, forming a hydroxyethyl‑lipoamide intermediate.

  2. Transfer of the acetyl group (E2): The acetyl group (2‑C) is transferred from the hydroxyethyl‑lipoamide to coenzyme A, producing acetyl‑CoA.

  3. Regeneration of lipoamide (E3): The reduced lipoamide is re‑oxidised by NAD⁺, yielding NADH + H⁺ and restoring the enzyme for another cycle.

Role of Coenzyme A (CoA‑SH)

Coenzyme A is a vital carrier molecule that functions as a “swinging arm” to transport the acetyl group from the enzyme complex to the next stage of respiration (the citric acid cycle). Its key features are:

  • Contains a reactive thiol group (‑SH) that forms a thioester bond with the acetyl group, creating acetyl‑CoA.

  • The thioester bond is a high‑energy linkage; its hydrolysis releases energy that drives subsequent reactions in the citric acid cycle.

  • CoA‑SH is regenerated after each cycle, allowing it to repeatedly accept acetyl groups.

Summary Table of the Link Reaction

ComponentFunction in the Link ReactionKey Products
Pyruvate dehydrogenase (E1)Decarboxylates pyruvate, forming hydroxyethyl‑lipoamideCO₂ (released)
Dihydrolipoamide transacetylase (E2)Transfers acetyl group to CoA‑SHAcetyl‑CoA
Dihydrolipoamide dehydrogenase (E3)Re‑oxidises lipoamide using NAD⁺NADH + H⁺
Coenzyme A (CoA‑SH)Accepts acetyl group, forming a high‑energy thioesterAcetyl‑CoA (entry substrate for the citric acid cycle)

Suggested diagram: Schematic of the pyruvate dehydrogenase complex showing the three enzyme subunits, the flow of the acetyl group to CoA‑SH, and the production of NADH and CO₂.

Why the Link Reaction Is Important

The link reaction serves as a bridge between glycolysis and the citric acid cycle, performing three essential functions:

  • It converts the 3‑carbon pyruvate into a 2‑carbon acetyl group that can enter the citric acid cycle.

  • It generates one molecule of NADH per pyruvate, contributing to the electron transport chain’s ATP yield.

  • It releases CO₂, a waste product that is expelled from the cell.

Key Points to Remember for A‑Level Exams

  1. Write the overall reaction correctly, including CoA‑SH and NAD⁺.

  2. Identify the three enzymes of the pyruvate dehydrogenase complex and their specific roles.

  3. Explain why the thioester bond in acetyl‑CoA is considered a high‑energy bond.

  4. State that each molecule of glucose yields two molecules of acetyl‑CoA (one from each pyruvate).