Beta oxidation

Beta oxidation is a metabolic process involving multiple steps by which fatty acid molecules are broken down within the mitochondria in eukaryotic cells, and in the cytoplasm of prokaryotic cells. This process generates acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain. It is named 'beta oxidation' because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group.

Process

Beta oxidation consists of four steps: dehydrogenation, hydration, another dehydrogenation, and finally thiolytic cleavage. Each step is facilitated by a specific enzyme.

1. Dehydrogenation: The first step in beta oxidation is the oxidation of the fatty acid by acyl-CoA dehydrogenase to create a trans double bond between the alpha and beta carbons. This process generates one molecule of FADH2.
2. Hydration: In the second step, water is added to the fatty acid by enoyl-CoA hydratase to form a beta-hydroxy group. This step is an example of stereospecificity, as only the L isomer of the molecule is produced.
3. Second Dehydrogenation: The third step is another oxidation, this time of the beta-hydroxy group to a keto group. This step is catalyzed by hydroxyacyl-CoA dehydrogenase, and generates one molecule of NADH.
4. Thiolytic Cleavage: The final step is the cleavage of the beta-ketoacyl CoA by thiolase, releasing an acetyl-CoA molecule and a fatty acid chain shortened by two carbon atoms.

Regulation

Beta oxidation is regulated by a number of factors, including the availability of fatty acids, the levels of malonyl-CoA, and the energy status of the cell. The rate of beta oxidation can be increased by exercise, fasting, and low-carbohydrate diets.

Clinical Significance

Defects in beta oxidation can lead to a number of metabolic disorders, including medium-chain acyl-CoA dehydrogenase deficiency (MCADD), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), and carnitine deficiency. These conditions can lead to symptoms such as hypoglycemia, lethargy, and muscle weakness, and can be life-threatening if not properly managed.

See Also

• Fatty acid metabolism
• Ketogenesis
• Citric acid cycle
• Electron transport chain

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