Beta oxidation is the process by which fatty acid molecules are broken down in the mitochondria to generate acetyl-coA, which enters the TCA cycle, and NADH and FADH2, which are used by the electron transport chain.
Fatty Acid Catabolism involve three stages. The first stage of fatty acid catabolism is Beta Oxidation. The second stage is acetyl CoA oxidation to carbon dioxide. The third stage is electron transfer from electron carriers to the electron transfer chain.
Priming the fatty acid for oxidation: Carnitine Shuttle
- Acyl CoA is transferred to the hydroxyl group of carnitine by carnitine palmitoyltransferase I (palmitoyltransferase) located on the outer mitochondrial membrane
- Acylcarnitine is shuttled inside by a carnitine-acylcarnitine translocase
- Acylcarnitine is converted back to acyl CoA by carnitine acyltransferase II (palmitoyltransferase) located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol.
Once the fatty acid is inside the mitochondrial matrix, Beta Oxidation can begin. It has 4 steps.
- Step 1 of Beta Oxidation: Long chain fatty acid is dehydrogenated to create a trans double bond between C2 and C3. This is catalyzed by the fatty acyl CoA dehydrogenase to produce trans-delta 2-enoyl CoA. It uses FAD as an electron acceptor and it is reduced to FADH2.
- Step 2 of Beta Oxidation: Trans-delta2-enoyl CoA is hydrated at the double bond to produce L-B-hydroxyacyl CoA. This is catalyzed by enoyl CoA hydratase.
- Step 3 of Beta Oxidation: L-B-hydroxyacyl CoA is dehydrogenated again to create B-ketoacyl CoA by B-hydroxyacyl CoA dehydrogenase. This enzyme uses NAD as an electron acceptor.
- Step 4 of Beta Oxidation: Thiolysis occurs between C2 and C3 (alpha and beta carbons) of B-ketoacyl CoA. Thiolase enzyme catalyzes the reaction when a new molecule of coenzyme A breaks the bond by nucleophilic attack on C3. This releases the first two carbon units, as acetyl CoA, and a fatty acyl CoA minus two carbons. The process continues until all of the carbons in the fatty acid are turned into acetyl CoA.
Fatty acids are oxidized by most of the tissues in the body. However, some tissues such as the adrenal medulla do not use fatty acids for their energy requirements and instead use carbohydrates.
References for Beta Oxidation: