Fatty Acid Oxidation (β-Oxidation) Study Notes

Fatty Acid Oxidation

Overview of Fatty Acid Oxidation

Fatty acid oxidation is a central metabolic pathway in biochemistry, allowing cells to extract energy from fatty acids. This process primarily occurs in the mitochondria and involves the breakdown of fatty acids into acetyl-CoA units, which can then enter the citric acid cycle for further energy production.

• Fats are used for energy and water storage, and can be broken down into glycerol and fatty acids.

• Glycerol can be converted to DHAP (dihydroxyacetone phosphate) to enter glycolysis, yielding ATP and NADH.

• Fatty acids undergo β-oxidation to enter the Citric Acid Cycle as acetyl-CoA.

Transport of Fatty Acids into the Mitochondria

Long-chain fatty acids require a specialized transport system to enter the mitochondrial matrix, where β-oxidation occurs.

• Fatty acids are activated by conversion to fatty acyl-CoA in the cytosol (requires ATP).

• Fatty acyl-CoA is transported into the mitochondrial matrix via the carnitine shuttle:

  • Carnitine acyltransferase I (outer mitochondrial membrane): Converts fatty acyl-CoA to acyl-carnitine.

  • Acyl-carnitine is transported across the inner mitochondrial membrane.

  • Carnitine acyltransferase II (inner mitochondrial membrane): Converts acyl-carnitine back to fatty acyl-CoA in the matrix.

β-Oxidation Pathway

β-Oxidation is the process by which fatty acids are broken down in the mitochondrial matrix, producing acetyl-CoA, NADH, and FADH2.

• Each cycle of β-oxidation shortens the fatty acid by two carbons, releasing one acetyl-CoA per cycle.

• The process repeats until the entire fatty acid is converted to acetyl-CoA units.

Steps of β-Oxidation

1. Oxidation by acyl-CoA dehydrogenase: Formation of a double bond between the α and β carbons, producing FADH2. $\text{Acyl-CoA} + \text{FAD} \rightarrow \text{trans-Δ}^2\text{-enoyl-CoA} + \text{FADH}_2$

2. Hydration by enoyl-CoA hydratase: Addition of water across the double bond. $\text{trans-Δ}^2\text{-enoyl-CoA} + \text{H}_2\text{O} \rightarrow \text{L-3-hydroxyacyl-CoA}$

3. Oxidation by hydroxyacyl-CoA dehydrogenase: Formation of a keto group, producing NADH. $\text{L-3-hydroxyacyl-CoA} + \text{NAD}^+ \rightarrow \text{3-ketoacyl-CoA} + \text{NADH} + \text{H}^+$

4. Thiolysis by thiolase: Cleavage of the bond, releasing acetyl-CoA and a shortened acyl-CoA. $\text{3-ketoacyl-CoA} + \text{CoA-SH} \rightarrow \text{Acetyl-CoA} + \text{Acyl-CoA (shortened by 2C)}$

Energy Yield from β-Oxidation

• Each round produces 1 FADH2, 1 NADH, and 1 acetyl-CoA.

• Acetyl-CoA enters the citric acid cycle, generating additional ATP.

Summary Table: β-Oxidation Steps and Products

Step	Enzyme	Product	Energy Carrier Produced
1. Oxidation	Acyl-CoA dehydrogenase	trans-Δ2-enoyl-CoA	FADH2
2. Hydration	Enoyl-CoA hydratase	L-3-hydroxyacyl-CoA	-
3. Oxidation	Hydroxyacyl-CoA dehydrogenase	3-ketoacyl-CoA	NADH
4. Thiolysis	Thiolase	Acetyl-CoA + Acyl-CoA (shortened)	-

Example: Palmitic Acid (C16) β-Oxidation

• Palmitic acid (16 carbons) undergoes 7 cycles of β-oxidation, yielding 8 acetyl-CoA, 7 FADH2, and 7 NADH.

• Each acetyl-CoA enters the citric acid cycle for further ATP production.

Additional info: The carnitine shuttle is essential for transporting long-chain fatty acids into the mitochondria, as short- and medium-chain fatty acids can diffuse directly.