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Beta-Oxidation of Fatty Acids
Beta-oxidation is a metabolic process that breaks down fatty acids into acetyl-CoA molecules, which can then be used to generate energy through the citric acid cycle and oxidative phosphorylation. It primarily occurs in the mitochondria of eukaryotic cells.
Steps of Beta-Oxidation:
Activation:
Fatty acids are activated by attaching a Coenzyme A (CoA) molecule to form fatty acyl-CoA. This reaction is catalyzed by fatty acyl-CoA synthetase and requires the expenditure of two high-energy phosphate bonds from ATP.
Transport into Mitochondria:
Long-chain fatty acyl-CoA molecules are transported into the mitochondrial matrix via the carnitine shuttle system. This involves the conversion of fatty acyl-CoA to fatty acylcarnitine, which can then cross the mitochondrial membrane.
Four-Step Oxidation Cycle:
The actual beta-oxidation process involves a series of four enzymatic reactions that repeatedly cleave two-carbon units from the fatty acyl-CoA chain, producing acetyl-CoA.
Oxidation: Acyl-CoA dehydrogenase catalyzes the oxidation of the alpha and beta carbons, forming a trans double bond and reducing FAD to FADH2.
Hydration: Enoyl-CoA hydratase adds a water molecule across the double bond, forming a hydroxyl group at the beta carbon.
Oxidation: L-3-hydroxyacyl-CoA dehydrogenase oxidizes the hydroxyl group to a carbonyl group, forming a ketoacyl-CoA and reducing NAD+ to NADH.
Thiolysis: Thiolase cleaves the ketoacyl-CoA molecule between the alpha and beta carbons, releasing acetyl-CoA and a shortened fatty acyl-CoA.
Repeat and Completion:
The shortened fatty acyl-CoA then undergoes further rounds of beta-oxidation until it is completely broken down into acetyl-CoA molecules.
Energy Yield:
Each round of beta-oxidation produces one molecule of acetyl-CoA, one FADH2, and one NADH.
Acetyl-CoA enters the citric acid cycle, generating more NADH and FADH2.
These electron carriers then donate their electrons to the electron transport chain, leading to the production of ATP through oxidative phosphorylation.
Regulation:
Beta-oxidation is regulated by various factors, including the availability of fatty acids, the energy status of the cell, and hormonal signals.
Key regulatory enzymes include carnitine palmitoyltransferase I (CPT I), which controls the entry of fatty acids into the mitochondria, and malonyl-CoA, which inhibits CPT I.
Significance of Beta-Oxidation:
Provides a major source of energy, especially during fasting or prolonged exercise when carbohydrate stores are depleted.
Helps maintain blood glucose levels by providing an alternative fuel source for tissues like the heart and skeletal muscle.
Plays a role in various metabolic disorders, including fatty acid oxidation disorders and obesity.