Omega Oxidation of Fatty Acids

Fatty acids are vital in our diet and are critical in numerous biological functions. They provide a major energy source and are essential for synthesizing important molecules like phospholipids and signaling compounds. Structurally, fatty acids comprise long hydrocarbon chains ending with the carboxyl group. 

1.0What are Fatty Acids?

Fatty acids are long-chain hydrocarbons with a carboxyl group (-COOH) at one end. They are key components of lipids in the body and can be classified into:

• Saturated Fatty Acids: These fatty acids have no double bonds between carbon atoms (e.g., stearic acid).  
• Unsaturated Fatty Acids: These fatty acids contain one or more double bonds. Examples include oleic acid for monounsaturated fatty acids and linoleic acid for polyunsaturated fatty acids.

2.0Pathways of Fatty Acid Oxidation

Fatty acids are primarily oxidized in the body through:

• Beta Oxidation: The main pathway for fatty acid catabolism occurs in the mitochondria, where fatty acids are broken down into acetyl-CoA units.
• Alpha Oxidation: Occurs in peroxisomes and is important for the degradation of branched-chain fatty acids.
• Omega Oxidation: A minor pathway in the endoplasmic reticulum, where the omega carbon (the last carbon of the fatty acid chain) undergoes oxidation.

3.0Omega Oxidation - Definition and Location

• Omega oxidation is a metabolic pathway that involves the oxidation of fatty acids' terminal (omega) carbon. 
• It occurs primarily in the endoplasmic reticulum of liver and kidney cells. 
• This pathway is an alternative route for fatty acid degradation, especially when beta-oxidation is impaired.

4.0Omega Oxidation of Fatty Acids Reaction

The process of omega oxidation involves the following steps:

• Fatty Acid Activation: The fatty acid is activated by coenzyme A to form fatty acyl-CoA.
• Hydroxylation: Cytochrome P450 enzymes introduce a hydroxyl group (-OH) at the omega carbon, forming an omega-hydroxy fatty acid.
• Dehydrogenation: The hydroxyl group is oxidized to a keto group (=O), resulting in an omega-keto fatty acid.
• Further Oxidation: The keto group is oxidized to a carboxyl group (-COOH), yielding a dicarboxylic acid.
• Beta Oxidation of Dicarboxylic Acids: The dicarboxylic acid can enter the beta-oxidation pathway or other metabolic pathways for further breakdown and energy production.

5.0Steps of Omega Oxidation (Flow Chart)

1. The pathway begins with the oxidation of the ω methyl group by mixed-function oxidases, which transfer oxygen from molecular oxygen with the help of cytochrome P450 and electron donor NADPH to oxidize methyl to –CH2OH. 

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2. In the next two steps the primary hydroxyl is oxidized to an acid by alcohol and aldehyde dehydrogenases to the carboxyl group. 

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3. The resultant dicarboxylic acid may undergo β oxidation from one or both ends. 

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4. The carboxyl group is activated and degraded by β oxidation in the mitochondria. Each round of oxidation releases acetylCoA and a shortened dicarboxylic acid. Some of these shortened products like succinic acid can enter the TCA cycle whereas others may be structural constituents of complex biomolecules.

6.0Biological Significance of Omega Oxidation

Omega oxidation is crucial for:

• Detoxification: Provides a route for the metabolism of xenobiotics and other fatty acids unsuitable for beta-oxidation.
• Energy Production: Serves as a secondary energy source when beta-oxidation is compromised.
• Regulation of Fatty Acid Levels: Helps maintain fatty acid homeostasis by degrading excess fatty acids.

7.0Omega - 3 Fatty Acids and Fish Oil

Omega-3 fatty acids are polyunsaturated fatty acids essential for human health. They include:

• Alpha-linolenic acid (ALA): Found in plant oils.
• Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are found in marine oils.
• Fish Oil: Rich in EPA and DHA, fish oil is known for its numerous health benefits, including:
• Brain Function: Supports cognitive function and may help in preventing neurodegenerative diseases.
• Anti-inflammatory Properties: Helps in managing inflammatory conditions such as arthritis.