Alpha-oxidation

Alpha-oxidation

Alpha-oxidation is a metabolic process involving the breakdown of fatty acids in the peroxisomes of cells. Unlike the more common beta-oxidation pathway, which removes two-carbon units from the carboxyl end of fatty acids, alpha-oxidation removes a single carbon atom from the carboxyl end. This process is particularly important for the metabolism of branched-chain fatty acids, such as phytanic acid, which cannot undergo beta-oxidation due to the presence of a methyl group on the beta carbon.

Mechanism

Alpha-oxidation occurs primarily in the peroxisomes and involves several enzymatic steps:

1. **Hydroxylation**: The first step is the hydroxylation of the alpha carbon of the fatty acid. This reaction is catalyzed by the enzyme phytanoyl-CoA hydroxylase, which requires molecular oxygen and iron as cofactors.
2. **Decarboxylation**: The hydroxylated fatty acid undergoes oxidative decarboxylation, resulting in the removal of the carboxyl group as carbon dioxide (CO₂). This step is catalyzed by the enzyme 2-hydroxyphytanoyl-CoA lyase.
3. **Conversion to Acyl-CoA**: The resulting product is converted into an acyl-CoA derivative, which can then enter the beta-oxidation pathway for further degradation.

Biological Significance

Alpha-oxidation is crucial for the metabolism of certain dietary fatty acids, particularly those derived from plant sources. The inability to properly metabolize phytanic acid due to defects in alpha-oxidation can lead to the accumulation of this fatty acid in tissues, resulting in disorders such as Refsum disease.

Clinical Implications

Deficiencies in the enzymes involved in alpha-oxidation can lead to metabolic disorders. For example, Refsum disease is characterized by the accumulation of phytanic acid in the blood and tissues, leading to symptoms such as peripheral neuropathy, cerebellar ataxia, and retinitis pigmentosa. Diagnosis is typically made through the measurement of phytanic acid levels in the blood, and treatment involves dietary restriction of phytanic acid.

Also see

• Beta-oxidation
• Peroxisome
• Fatty acid metabolism
• Refsum disease
• Phytanic acid