Fatty acid oxidation is a crucial process in energy metabolism. It breaks down fatty acids into acetyl-CoA units, providing a significant source of energy for cells. This process involves transporting fatty acids into mitochondria and a series of chemical reactions known as beta-oxidation.
The breakdown of fatty acids yields more energy per gram than carbohydrates or proteins. Understanding fatty acid oxidation is key to grasping how our bodies use stored fat for fuel, especially during fasting or extended physical activity.
Fatty Acid Transport and Activation
Carnitine Shuttle System
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- Long-chain fatty acids cannot directly cross the inner mitochondrial membrane
- Carnitine shuttle system facilitates transport of fatty acids into mitochondria
- Carnitine palmitoyltransferase I (CPT I) catalyzes formation of acylcarnitine from acyl-CoA and carnitine
- Carnitine-acylcarnitine translocase moves acylcarnitine across inner mitochondrial membrane
- Carnitine palmitoyltransferase II (CPT II) converts acylcarnitine back to acyl-CoA inside mitochondria
- Free carnitine returns to cytosol for reuse
Fatty Acid Activation and Dehydrogenation
- Fatty acids activated to acyl-CoA by acyl-CoA synthetase in cytosol
- Activation requires ATP and produces AMP and pyrophosphate
- Acyl-CoA dehydrogenase catalyzes first step of beta-oxidation inside mitochondria
- Enzyme removes two hydrogen atoms from acyl-CoA, forming a double bond
- Process generates FADH2 from FAD, an important electron carrier
- FADH2 transfers electrons to electron transport chain, contributing to ATP production
- NADH produced in subsequent steps of beta-oxidation, another crucial electron carrier
Beta-Oxidation Cycle
Four-Step Process of Beta-Oxidation
- Beta-oxidation breaks down fatty acids into acetyl-CoA units
- Process occurs in mitochondrial matrix
- Consists of four repeating steps: oxidation, hydration, oxidation, and thiolysis
- Each cycle shortens fatty acid chain by two carbon atoms
- Acyl-CoA dehydrogenase catalyzes first oxidation step, forming trans-2-enoyl-CoA
- Enoyl-CoA hydratase adds water to double bond, producing 3-hydroxyacyl-CoA
- 3-hydroxyacyl-CoA dehydrogenase oxidizes hydroxyl group, forming 3-ketoacyl-CoA
- Thiolase cleaves 3-ketoacyl-CoA, releasing acetyl-CoA and shortened acyl-CoA
Energy Yield and Regulation
- Each cycle produces one FADH2, one NADH, and one acetyl-CoA
- FADH2 and NADH feed into electron transport chain for ATP production
- Acetyl-CoA enters citric acid cycle for further oxidation
- Process regulated by availability of fatty acids and energy demand
- Malonyl-CoA inhibits carnitine palmitoyltransferase I, controlling fatty acid entry into mitochondria
- Hormone-sensitive lipase in adipose tissue regulates fatty acid release into bloodstream
Ketone Body Formation
Ketogenesis Process
- Ketone bodies form when acetyl-CoA accumulates beyond capacity of citric acid cycle
- Occurs during fasting, low-carbohydrate diets, or uncontrolled diabetes
- Three main ketone bodies: acetoacetate, β-hydroxybutyrate, and acetone
- Acetoacetate synthesized from two acetyl-CoA molecules
- β-hydroxybutyrate formed by reduction of acetoacetate
- Acetone produced by spontaneous decarboxylation of acetoacetate
Ketone Body Utilization and Metabolism
- Ketone bodies serve as alternative fuel source for brain and other tissues
- Brain can derive up to 70% of its energy from ketone bodies during prolonged fasting
- Liver cannot use ketone bodies due to lack of necessary enzymes
- Extrahepatic tissues convert ketone bodies back to acetyl-CoA for energy production
- Excessive ketone body production leads to ketoacidosis, a potentially dangerous condition
- Insulin regulates ketone body production by controlling fatty acid release from adipose tissue