Beta-oxidation
Overview
Beta-oxidation is a metabolic process that involves the breakdown of fatty acids into acetyl-CoA, a substrate for the citric acid cycle. This process occurs in the mitochondria of eukaryotic cells and the peroxisomes of plants. It is a crucial part of lipid metabolism, providing a significant source of ATP for cells, particularly in times of fasting or prolonged exercise.
Biochemistry of Beta-Oxidation
The process of beta-oxidation involves a series of enzymatic reactions. The first step is the activation of the fatty acid by the enzyme fatty acyl-CoA synthetase, which converts the fatty acid into a fatty acyl-CoA ester. This reaction requires ATP and results in the release of a molecule of AMP and pyrophosphate.
The fatty acyl-CoA is then transported into the mitochondria by the carnitine shuttle system. Inside the mitochondria, the fatty acyl-CoA undergoes a series of four reactions catalysed by specific enzymes. These reactions are:
1. Dehydrogenation by fatty acyl-CoA dehydrogenase, resulting in a trans double bond between the alpha and beta carbons and the production of FADH2. 2. Hydration by enoyl-CoA hydratase, which adds a water molecule across the double bond. 3. Another dehydrogenation by 3-hydroxyacyl-CoA dehydrogenase, producing NADH. 4. Thiolysis by beta-ketothiolase, which cleaves the beta-ketoacyl-CoA, releasing a molecule of acetyl-CoA and a shortened fatty acyl-CoA.
These reactions are repeated, each cycle shortening the fatty acyl-CoA by two carbon atoms until the entire fatty acid chain has been converted into acetyl-CoA.
Energy Production
The acetyl-CoA produced by beta-oxidation enters the citric acid cycle, where it is further oxidized to produce ATP. Each round of the citric acid cycle generates three NADH, one FADH2, and one GTP. The NADH and FADH2 donate their electrons to the electron transport chain, driving the synthesis of ATP through oxidative phosphorylation.
In addition to the ATP produced by the citric acid cycle and oxidative phosphorylation, the initial activation of the fatty acid also generates a small amount of ATP. Thus, the total ATP yield from the beta-oxidation of a fatty acid depends on the length of the fatty acid chain.
Regulation of Beta-Oxidation
The rate of beta-oxidation is regulated by several factors. The availability of fatty acids is a major determinant of the rate of beta-oxidation. Hormones such as insulin and glucagon also play a role in the regulation of this process. Insulin inhibits beta-oxidation by promoting the storage of fatty acids in adipose tissue, while glucagon stimulates beta-oxidation by promoting the release of fatty acids from adipose tissue.
The enzymes involved in beta-oxidation are also subject to regulation. For example, the activity of carnitine palmitoyltransferase I, the enzyme that controls the entry of fatty acyl-CoA into the mitochondria, is inhibited by malonyl-CoA, a signal of abundant carbohydrate availability.
Clinical Significance
Defects in the enzymes involved in beta-oxidation can lead to a variety of metabolic disorders. These disorders are typically characterized by hypoglycemia, hypoketosis, and the accumulation of fatty acids or their metabolites in tissues. Examples of such disorders include medium-chain acyl-CoA dehydrogenase deficiency and carnitine deficiency.