The primary pathway for fatty acid catabolism is the β-oxidation pathway, which breaks down fatty acids into acetyl-CoA. Here’s a detailed look at this process:
Overview of β-Oxidation
The β-oxidation pathway is the key metabolic process for the breakdown of fatty acids, enabling the body to derive energy from these stored lipids. This pathway occurs mainly in the mitochondria and involves a series of repeated steps.
Step 1: Activation of Fatty Acid
- Location: Cytosol and outer mitochondrial membrane
- Process: Before β-oxidation can begin, fatty acids must be activated. This involves converting the fatty acid into a fatty acyl-CoA molecule. The enzyme responsible for this reaction is located on the outer mitochondrial membrane.
- Details: The reaction uses ATP to form a high-energy thioester bond between the fatty acid and Coenzyme A.
Step 2: Transport into Mitochondria
- Location: Mitochondrial matrix
- Process: The fatty acyl-CoA is transported across the inner mitochondrial membrane into the mitochondrial matrix, where β-oxidation takes place. This transport process often involves the carnitine shuttle system, especially for long-chain fatty acids.
Step 3: β-Oxidation Proper
Once inside the mitochondria, fatty acyl-CoA undergoes a series of four key reactions that are repeated until the fatty acid is fully broken down into acetyl-CoA units:
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Oxidation: The fatty acyl-CoA is oxidized, generating a trans-α,β-unsaturated acyl-CoA and producing FADH2.
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Hydration: Water is added to the trans-α,β-unsaturated acyl-CoA, yielding a β-hydroxyacyl-CoA.
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Oxidation: The β-hydroxyacyl-CoA is further oxidized, producing a β-ketoacyl-CoA and generating NADH.
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Thiolysis: The β-ketoacyl-CoA is cleaved by thiolase, producing acetyl-CoA and a fatty acyl-CoA that is two carbons shorter than the initial one.
- This shortened fatty acyl-CoA can now re-enter the β-oxidation cycle.
- The acetyl-CoA molecules produced can enter the citric acid cycle (Krebs cycle) for further oxidation and ATP generation.
Significance of β-Oxidation
The β-oxidation pathway is crucial for:
- Energy Production: It’s a primary source of energy, particularly when carbohydrates are scarce.
- Fuel Storage: Breakdown of stored fats provides energy during fasting or prolonged exercise.
- Ketone Body Formation: During fasting or in uncontrolled diabetes, excessive β-oxidation can lead to the formation of ketone bodies.
Summary Table
| Step | Location | Process | Products |
|---|---|---|---|
| Fatty Acid Activation | Cytosol/Outer Mitochondria | Fatty acid is converted to fatty acyl-CoA using ATP. | Fatty acyl-CoA |
| Transport into Mitochondria | Mitochondrial Matrix | Fatty acyl-CoA is transported into the mitochondria, often via the carnitine shuttle system. | Fatty acyl-CoA within the matrix |
| Oxidation | Mitochondrial Matrix | Fatty acyl-CoA is oxidized, forming FADH2. | trans-α,β-unsaturated acyl-CoA, FADH2 |
| Hydration | Mitochondrial Matrix | Water is added to trans-α,β-unsaturated acyl-CoA. | β-hydroxyacyl-CoA |
| Oxidation | Mitochondrial Matrix | β-hydroxyacyl-CoA is oxidized, forming NADH. | β-ketoacyl-CoA, NADH |
| Thiolysis | Mitochondrial Matrix | β-ketoacyl-CoA is cleaved, releasing acetyl-CoA and a two-carbon shorter fatty acyl-CoA. | Acetyl-CoA, shortened fatty acyl-CoA |
