Mitochondrial Respiration
Aerobic cellular respiration is split into four distinct stages: Glycolysis, the Link Reaction, the Krebs Cycle, and Oxidative Phosphorylation. In this guide, we map the pathways occurring inside the **mitochondrial matrix** that generate the coenzymes needed to fuel ATP production.
Step-by-Step Biochemical Steps
Learn the exact sequence of events starting from pyruvate transport:
The Link Reaction
Pyruvate ($3\text{C}$) produced in glycolysis is actively transported from the cytoplasm into the mitochondrial matrix. It undergoes **decarboxylation** (losing $\text{CO}_2$) and **dehydrogenation** (losing $\text{H}$ to reduce $\text{NAD}$ to $\text{NADH}$), reacting with Coenzyme A to form Acetyl Coenzyme A ($2\text{C}$).
Formation of Citrate ($6\text{C}$)
Acetyl CoA ($2\text{C}$) combines with the $4\text{C}$ acceptor molecule, Oxaloacetate, to form Citrate ($6\text{C}$). Coenzyme A is released and recycled back to the Link Reaction.
Decarboxylation & Dehydrogenation of Citrate
Citrate ($6\text{C}$) is converted into a $5\text{C}$ intermediate, losing a molecule of carbon dioxide ($\text{CO}_2$) and a pair of hydrogen atoms, which reduce another $\text{NAD}$ to $\text{NADH}$.
Regeneration of Oxaloacetate ($4\text{C}$)
The $5\text{C}$ intermediate is converted back to Oxaloacetate ($4\text{C}$) through a series of reactions. This stage yields:
• One $\text{CO}_2$ molecule.
• Two reduced $\text{NAD}$ ($\text{NADH}$).
• One reduced $\text{FAD}$ ($\text{FADH}_2$).
• One ATP molecule synthesized via **substrate-level phosphorylation**.
Summary of Yields (Per Glucose Molecule)
Since one glucose molecule yields two pyruvate molecules during glycolysis, the Link Reaction and Krebs Cycle turn **twice** per glucose molecule:
| Output Quantity | Per Pyruvate (1 Turn) | Per Glucose (2 Turns) |
|---|---|---|
| Reduced NAD ($\text{NADH}$) | 4 ($1$ from Link, $3$ from Krebs) | 8 ($2$ from Link, $6$ from Krebs) |
| Reduced FAD ($\text{FADH}_2$) | 1 | 2 |
| Carbon Dioxide ($\text{CO}_2$) | 3 ($1$ from Link, $2$ from Krebs) | 6 ($2$ from Link, $4$ from Krebs) |
| ATP (Direct Yield) | 1 | 2 |
Worked Exam Example
Worked A-Level Example
Question: Explain the significance of the Krebs Cycle in aerobic respiration, specifically regarding its role in generating ATP.
Solution:
- The Krebs Cycle directly produces a small amount of ATP ($2$ molecules per glucose) via **substrate-level phosphorylation**.
- The primary role of the Krebs Cycle is to produce **reduced NAD ($\text{NADH}$)** and **reduced FAD ($\text{FADH}_2$)**.
- These reduced coenzymes carry hydrogen atoms (protons and electrons) to the inner mitochondrial membrane (**cristae**).
- The electrons enter the **Electron Transport Chain (ETC)**, releasing energy to drive chemiosmosis and synthesize a large amount of ATP ($28-30$ molecules) via **oxidative phosphorylation**.
Frequently Asked Questions
Although the Krebs Cycle does not use oxygen directly, it requires oxidized NAD and FAD to proceed. If oxygen is absent, the Electron Transport Chain stops, meaning reduced NAD and FAD cannot be oxidized back. This depletes the cell's pool of oxidized NAD and FAD, causing the Link Reaction and Krebs Cycle to halt.
Glycolysis splits glucose into pyruvate in the cytoplasm. The Link Reaction converts pyruvate into Acetyl CoA, which enters the mitochondrial matrix to join the Krebs Cycle, acting as the bridge between anaerobic cytoplasmic reactions and aerobic mitochondrial reactions.
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