# The Link Reaction ## Overview - Pyruvate is the end product of glycolysis that still contains substantial chemical energy - When oxygen is available, pyruvate enters the mitochondrial matrix to continue aerobic respiration - This transition stage is called the **link reaction** because it connects glycolysis (in the cytoplasm) to the Krebs cycle (in the matrix)

The link reaction is the process where pyruvate from glycolysis is converted into acetyl coenzyme A in the mitochondrial matrix

## Transport of Pyruvate into the Mitochondria - Pyruvate moves from the cytoplasm across the double membrane of the mitochondria - This transport occurs via **active transport** - Requires a specific transport protein embedded in the membrane - Uses a small amount of ATP to move pyruvate against its concentration gradient - Think of it like paying a toll to cross a bridge - pyruvate needs to spend some energy (ATP) to get access to the mitochondrial matrix where the action happens ## The Steps of the Link Reaction The link reaction involves two main chemical transformations: ### Step 1: Decarboxylation and Dehydrogenation - Pyruvate (3C) is **oxidised** by enzymes - A carbon atom is removed as carbon dioxide ($\text{CO}_2$) - Hydrogen atoms are removed and transferred to the coenzyme NAD - This produces: - Acetate ($\text{CH}_3\text{CO(O)}^-$) - a 2-carbon compound - Carbon dioxide ($\text{CO}_2$) - released as a waste product - Reduced NAD (NADH) - carries hydrogen to later stages $$\text{pyruvate} + \text{NAD}^+ \rightarrow \text{acetate} + \text{CO}_2 + \text{NADH}$$ ### Step 2: Combination with Coenzyme A - The acetate (2C) combines with **coenzyme A (CoA)** - This forms **acetyl coenzyme A** (often written as acetyl CoA) - Acetyl CoA is now ready to enter the Krebs cycle $$\text{acetate} + \text{CoA} \rightarrow \text{acetyl CoA}$$ ## Products of the Link Reaction For each pyruvate molecule that enters, the link reaction produces: | Product | Description | |---------|-------------| | **Acetyl CoA** | 2-carbon acetyl group attached to coenzyme A; enters Krebs cycle | | **Carbon dioxide ($\text{CO}_2$)** | Waste gas that diffuses out of the cell | | **Reduced NAD (NADH)** | Hydrogen carrier that transports H atoms to oxidative phosphorylation | ### Overall Equation $$\text{pyruvate} + \text{NAD}^+ + \text{CoA} \rightarrow \text{acetyl CoA} + \text{CO}_2 + \text{NADH}$$ ## The Role of Coenzyme A

A coenzyme is a molecule that assists an enzyme in carrying out its function but is not consumed in the reaction itself

- Coenzyme A is composed of: - A nucleoside (ribose sugar + adenine base) - A vitamin derivative - In the link reaction, CoA acts like a molecular taxi: - It binds to the 2-carbon acetyl group that remains after pyruvate loses $\text{CO}_2$ - It transports this acetyl group into the Krebs cycle - Once delivered, CoA is released and can be reused - This is crucial because it brings the carbon skeleton from the original glucose molecule (or other respiratory substrates like lipids and amino acids) into the later stages of respiration - CoA essentially **links** the breakdown pathways in the cytoplasm to the energy-generating pathways in the mitochondria ## Important: Per Glucose Molecule

Remember that one glucose molecule produces two pyruvate molecules in glycolysis, so the link reaction happens twice per glucose

For **one glucose molecule** going through respiration: - **2 pyruvate** molecules enter the link reaction - **2 acetyl CoA** molecules are produced - **2 $\text{CO}_2$** molecules are released - **2 NADH** molecules are generated Think of it like processing two identical shipments - everything happens in duplicate. ## Summary: The Bridge Between Stages The link reaction serves as a critical connector: 1. **Before**: Glycolysis in the cytoplasm splits glucose into two 3-carbon pyruvate molecules 2. **During**: The link reaction in the mitochondrial matrix converts pyruvate (3C) into acetyl CoA (2C) 3. **After**: Acetyl CoA enters the Krebs cycle where the remaining carbons are fully oxidised | Stage | Location | Input | Output | |-------|----------|-------|--------| | Glycolysis | Cytoplasm | Glucose (6C) | 2 × Pyruvate (3C) | | **Link Reaction** | **Mitochondrial matrix** | **2 × Pyruvate (3C)** | **2 × Acetyl CoA (2C)** | | Krebs cycle | Mitochondrial matrix | 2 × Acetyl CoA (2C) | $\text{CO}_2$, NADH, FADH$_2$, ATP | ## Key Concepts to Remember - **Decarboxylation**: Removal of carbon as $\text{CO}_2$ - This is why you breathe out carbon dioxide when you respire - In the link reaction, one $\text{CO}_2$ is released per pyruvate - **Dehydrogenation**: Removal of hydrogen atoms - The hydrogen is picked up by NAD to form NADH - These hydrogens will eventually power ATP synthesis - **Active transport requirement**: Getting pyruvate into the mitochondria costs energy - Shows how important compartmentalisation is in cells - The mitochondria must carefully control what enters - **No ATP produced**: Unlike glycolysis and the Krebs cycle, the link reaction doesn't directly produce ATP - However, the NADH produced will generate ATP later during oxidative phosphorylation - The link reaction's main job is preparation, not immediate energy release