Fatty acid degradation
Fatty Acid Degradation
Fatty acid degradation is a metabolic process that involves the breakdown of fatty acids to generate acetyl-CoA, which can then enter the citric acid cycle to produce ATP. This process is crucial for energy production, especially in tissues such as the liver and muscle where fatty acids are a major source of energy.
Overview
Fatty acid degradation primarily occurs in the mitochondria of cells through a series of reactions known as beta-oxidation. This process involves the sequential removal of two-carbon units from the fatty acid chain, resulting in the production of acetyl-CoA, NADH, and FADH2. These products are then utilized in the electron transport chain to generate ATP.
Steps of Fatty Acid Degradation
Activation
The first step in fatty acid degradation is the activation of the fatty acid. This occurs in the cytosol and involves the conversion of the fatty acid into a fatty acyl-CoA thioester. This reaction is catalyzed by the enzyme acyl-CoA synthetase and requires the hydrolysis of ATP to AMP and pyrophosphate.
Transport into Mitochondria
Once activated, the fatty acyl-CoA must be transported into the mitochondria. This is achieved through the carnitine shuttle, which involves the conversion of the fatty acyl-CoA to a fatty acyl-carnitine by the enzyme carnitine acyltransferase I. The fatty acyl-carnitine is then transported across the mitochondrial membrane by a translocase enzyme and converted back to fatty acyl-CoA by carnitine acyltransferase II.
Beta-Oxidation
Inside the mitochondria, the fatty acyl-CoA undergoes beta-oxidation, which consists of four main steps:
1. Dehydrogenation: The fatty acyl-CoA is oxidized by acyl-CoA dehydrogenase, producing a trans double bond between the alpha and beta carbon atoms and generating FADH2.
2. Hydration: The trans double bond is hydrated by enoyl-CoA hydratase, forming a beta-hydroxyacyl-CoA.
3. Dehydrogenation: The beta-hydroxyacyl-CoA is oxidized by beta-hydroxyacyl-CoA dehydrogenase, producing NADH and a beta-ketoacyl-CoA.
4. Thiolysis: The beta-ketoacyl-CoA is cleaved by thiolase, releasing acetyl-CoA and a shortened acyl-CoA.
This cycle repeats until the entire fatty acid chain is converted into acetyl-CoA units.
Energy Yield
The complete oxidation of a fatty acid molecule yields a significant amount of ATP. For example, the oxidation of palmitic acid, a 16-carbon saturated fatty acid, produces 106 molecules of ATP.
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Contributors: Prab R. Tumpati, MD