Model Answer
0 min readIntroduction
β-oxidation is the catabolic process by which fatty acid molecules are broken down in the mitochondria and peroxisomes to generate acetyl-CoA, which can then be used in the citric acid cycle to produce energy. This pathway is vital for energy production, particularly during periods of fasting or prolonged exercise when glucose availability is limited. It’s a cyclical process that shortens the fatty acid chain by two carbon atoms with each turn, ultimately converting fats into a usable energy source. Understanding β-oxidation is fundamental to comprehending lipid metabolism and its role in maintaining energy homeostasis.
Overview of β-oxidation
β-oxidation is the primary pathway for the breakdown of fatty acids. It occurs primarily within the mitochondrial matrix in eukaryotes, although very long-chain fatty acids undergo initial oxidation in the peroxisomes. The process involves a series of four repeating enzymatic reactions that cleave two-carbon units from the carboxyl end of the fatty acid.
The Four Steps of β-oxidation
Each cycle of β-oxidation consists of the following four steps:
- Oxidation: Acyl-CoA dehydrogenase catalyzes the oxidation of acyl-CoA to trans-Δ2-enoyl-CoA, introducing a double bond between the α and β carbons. This reaction generates FADH2. Different acyl-CoA dehydrogenases exist for short, medium, and long-chain fatty acids.
- Hydration: Enoyl-CoA hydratase adds water across the double bond, forming L-β-hydroxyacyl-CoA.
- Oxidation: β-hydroxyacyl-CoA dehydrogenase oxidizes L-β-hydroxyacyl-CoA to β-ketoacyl-CoA, generating NADH.
- Thiolysis: β-ketothiolase cleaves β-ketoacyl-CoA, releasing acetyl-CoA and a shortened acyl-CoA molecule. This acyl-CoA then re-enters the cycle, repeating the four steps until the fatty acid is completely broken down.
Energetics of β-oxidation
The complete oxidation of one molecule of palmitic acid (a 16-carbon saturated fatty acid) yields:
- 8 molecules of acetyl-CoA
- 7 molecules of FADH2
- 7 molecules of NADH
These coenzymes are then used in the citric acid cycle and oxidative phosphorylation to generate ATP. Approximately 106 ATP molecules are produced from the complete oxidation of one palmitic acid molecule (as of knowledge cutoff 2023).
Regulation of β-oxidation
β-oxidation is regulated by several factors:
- Carnitine Shuttle: The transport of long-chain fatty acids into the mitochondrial matrix is mediated by the carnitine shuttle. This is a rate-limiting step and is regulated by malonyl-CoA, an intermediate in fatty acid synthesis. High levels of malonyl-CoA inhibit carnitine acyltransferase I, preventing fatty acid entry into the mitochondria.
- Hormonal Control: Hormones like insulin, glucagon, and epinephrine influence β-oxidation. Insulin inhibits β-oxidation, while glucagon and epinephrine stimulate it.
- NADH/NAD+ and FADH2/FAD ratios: High levels of NADH and FADH2 inhibit the dehydrogenases involved in β-oxidation, indicating sufficient energy levels.
Peroxisomal β-oxidation
Very long-chain fatty acids (longer than 22 carbons) are primarily oxidized in peroxisomes. Peroxisomal β-oxidation differs from mitochondrial β-oxidation in several ways:
- The first step is catalyzed by acyl-CoA oxidase, which produces hydrogen peroxide (H2O2) as a byproduct.
- Peroxisomal β-oxidation does not directly produce ATP.
- The shortened acyl-CoA molecules produced in peroxisomes are then transported to the mitochondria for further oxidation.
Clinical Significance
Defects in β-oxidation can lead to various metabolic disorders, such as:
- Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: This is a common inherited metabolic disorder that prevents the breakdown of medium-chain fatty acids. It can cause hypoglycemia, lethargy, and even sudden death, particularly during periods of fasting.
- Carnitine deficiency: This can impair the transport of fatty acids into the mitochondria, leading to energy deficits.
Conclusion
β-oxidation is a critical metabolic pathway for energy production from fatty acids. Its cyclical nature, regulated steps, and compartmentalization within mitochondria and peroxisomes ensure efficient and controlled lipid metabolism. Understanding the intricacies of this process is crucial for comprehending metabolic disorders and developing strategies to address them. Further research into the regulation and optimization of β-oxidation could offer potential therapeutic avenues for metabolic diseases and energy imbalances.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.