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How Does Fatty Acid Breakdown Occur?

Published in Fatty Acid Metabolism 3 mins read

Fatty acid breakdown, a process also known as beta-oxidation, involves a biochemical pathway that metabolizes fatty acids into usable energy molecules.

The Carnitine Shuttle and Fatty Acid Breakdown

The breakdown of fatty acids relies on the Carnitine Shuttle system. The reference "Fatty Acid Breakdown (Carnitine Shuttle)" highlights that this process is crucial for transporting fatty acids across the inner mitochondrial membrane, enabling them to be broken down for energy. This process usually occurs in the liver.

Key Steps in Fatty Acid Breakdown:

While the reference only mentions the importance of the Carnitine Shuttle and its location, a more complete explanation of fatty acid breakdown (beta-oxidation) includes the following steps which occur within the mitochondria:

  1. Activation: Fatty acids are activated in the cytosol by combining with Coenzyme A (CoA), forming fatty acyl-CoA. This step consumes ATP.

  2. Transport via Carnitine Shuttle: Because fatty acyl-CoA cannot directly cross the inner mitochondrial membrane, it is converted to fatty acyl-carnitine by carnitine palmitoyltransferase I (CPT-I), located on the outer mitochondrial membrane. The fatty acyl-carnitine is then transported across the inner mitochondrial membrane by a translocase. Once inside, carnitine palmitoyltransferase II (CPT-II) regenerates fatty acyl-CoA and releases carnitine. The carnitine returns to the cytosol to pick up another fatty acyl group.

  3. Beta-Oxidation: This cyclical process occurs in the mitochondrial matrix and involves four repeating reactions:

    • Oxidation: Fatty acyl-CoA is oxidized by acyl-CoA dehydrogenase, producing a double bond between the α and β carbons and generating FADH2.
    • Hydration: Enoyl-CoA hydratase adds water across the double bond, forming β-hydroxyacyl-CoA.
    • Oxidation: β-hydroxyacyl-CoA is oxidized by β-hydroxyacyl-CoA dehydrogenase, generating NADH and β-ketoacyl-CoA.
    • Cleavage (Thiolysis): β-ketoacyl-CoA is cleaved by thiolase (acyl-CoA acetyltransferase), releasing acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms.
  4. Repetition: The shortened fatty acyl-CoA then re-enters the beta-oxidation cycle, repeating the four reactions until the fatty acid is completely broken down into acetyl-CoA molecules.

  5. Acetyl-CoA Processing: Acetyl-CoA enters the citric acid cycle (Krebs cycle) to be further oxidized to CO2, generating more ATP. The FADH2 and NADH produced during beta-oxidation donate their electrons to the electron transport chain to generate even more ATP through oxidative phosphorylation.

Significance:

Fatty acid breakdown is crucial for:

  • Energy Production: Provides a significant source of energy, especially during fasting or prolonged exercise.
  • Regulation: Helps regulate energy homeostasis in the body.

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