Model Answer
0 min readIntroduction
β-oxidation, also known as fatty acid oxidation, is a catabolic process by which fatty acids are broken down in mitochondria and adjacent peroxisomes to generate acetyl-CoA, NADH, and FADH2. These products can then enter the citric acid cycle (Krebs cycle) to produce ATP, providing a significant energy source for the body, particularly during periods of fasting or prolonged exercise. This pathway is vital for organisms that utilize fats as a major energy reserve. The process is particularly important in tissues with high energy demands, such as muscle and liver.
β-Oxidation of Saturated Fatty Acids: A Step-by-Step Description
The β-oxidation pathway involves a repetitive series of four enzymatic reactions that shorten a saturated fatty acid by two carbon atoms at a time, releasing one molecule of acetyl-CoA in each cycle. Let's examine each step in detail:
Step 1: Activation of Fatty Acid
Before β-oxidation can begin, the fatty acid must be activated in the cytosol. This involves the attachment of coenzyme A (CoA) to the fatty acid, forming fatty acyl-CoA. This reaction is catalyzed by acyl-CoA synthetase and requires ATP. The resulting fatty acyl-CoA is then transported into the mitochondrial matrix by the carnitine shuttle.
Step 2: Transport into Mitochondria (Carnitine Shuttle)
The inner mitochondrial membrane is impermeable to long-chain fatty acyl-CoA. Therefore, a shuttle system is required. Carnitine palmitoyltransferase I (CPT I), located on the outer mitochondrial membrane, catalyzes the transfer of the fatty acyl group from CoA to carnitine, forming acylcarnitine. Acylcarnitine is then transported across the inner mitochondrial membrane by carnitine acylcarnitine translocase. Once inside the matrix, carnitine palmitoyltransferase II (CPT II) regenerates fatty acyl-CoA and releases carnitine, which is shuttled back to the intermembrane space.
Step 3: First Oxidation – Formation of trans-Δ2-Enoyl-CoA
This is the first oxidation step, catalyzed by acyl-CoA dehydrogenase. It introduces a double bond between the α and β carbons of the fatty acyl-CoA, forming trans-Δ2-enoyl-CoA. Different isoforms of acyl-CoA dehydrogenase exist, specific for short-, medium-, and long-chain fatty acids. This reaction also generates FADH2, which is subsequently oxidized by the electron transport chain to produce ATP.
Step 4: Hydration – Formation of L-β-Hydroxyacyl-CoA
trans-Δ2-enoyl-CoA is then hydrated by enoyl-CoA hydratase, adding water across the double bond to form L-β-hydroxyacyl-CoA.
Step 5: Second Oxidation – Formation of β-Ketoacyl-CoA
L-β-hydroxyacyl-CoA is dehydrogenated by β-hydroxyacyl-CoA dehydrogenase, oxidizing the β-hydroxy group to a β-keto group, forming β-ketoacyl-CoA. This reaction generates NADH.
Step 6: Cleavage – Formation of Acetyl-CoA and a Shorter Fatty Acyl-CoA
Finally, β-ketoacyl-CoA is cleaved by thiolase (acyl-CoA acetyltransferase), releasing acetyl-CoA and a fatty acyl-CoA molecule that is two carbon atoms shorter than the original. This shorter fatty acyl-CoA then re-enters the β-oxidation pathway, repeating the cycle until the fatty acid is completely broken down into acetyl-CoA molecules.
Overall ATP Yield: Each cycle of β-oxidation yields 1 FADH2, 1 NADH, and 1 acetyl-CoA. The acetyl-CoA enters the citric acid cycle, generating approximately 10 ATP molecules per cycle. Considering the electrons from FADH2 and NADH entering the electron transport chain, a 16-carbon fatty acid (palmitic acid) yields approximately 106 ATP molecules.
| Step | Enzyme | Reactant | Product | Cofactor |
|---|---|---|---|---|
| 1 | Acyl-CoA Synthetase | Fatty Acid + CoA + ATP | Fatty Acyl-CoA + AMP + PPi | ATP |
| 3 | Acyl-CoA Dehydrogenase | Fatty Acyl-CoA | trans-Δ2-Enoyl-CoA | FAD |
| 4 | Enoyl-CoA Hydratase | trans-Δ2-Enoyl-CoA | L-β-Hydroxyacyl-CoA | H2O |
| 5 | β-Hydroxyacyl-CoA Dehydrogenase | L-β-Hydroxyacyl-CoA | β-Ketoacyl-CoA | NAD+ |
| 6 | Thiolase | β-Ketoacyl-CoA | Acetyl-CoA + Shorter Fatty Acyl-CoA | CoA |
Conclusion
In conclusion, β-oxidation is a vital metabolic pathway for energy production from fatty acids. The cyclical process, involving four key enzymatic steps, efficiently breaks down saturated fatty acids into acetyl-CoA, NADH, and FADH<sub>2</sub>, ultimately contributing to substantial ATP generation. Understanding this pathway is crucial for comprehending lipid metabolism and its role in maintaining energy homeostasis within the body. Disruptions in β-oxidation can lead to various metabolic disorders, highlighting its clinical significance.
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.