Introduction:
Beta oxidation (β-oxidation) is the primary pathway for the degradation of fatty acids in the body. This process occurs inside the mitochondrial matrix, where acyl-CoA molecules are systematically broken down into acetyl-CoA units. These acetyl-CoA molecules then enter the citric acid cycle (TCA cycle) to generate energy in the form of ATP.
In simple terms, beta oxidation involves the sequential removal of two-carbon fragments from the carboxy end of fatty acyl-CoA molecules. The process gets its name because oxidation occurs at the beta carbon (the third carbon from the carboxyl end) of the fatty acid chain.
Definition of Beta Oxidation
Beta oxidation is defined as the stepwise degradation of fatty acids or acyl-CoAs by removing two-carbon fragments (as acetyl-CoA) from the carboxy terminus, after oxidation of the β-carbon to the keto form. It involves a series of four key reactions that repeat until the entire fatty acid is converted to acetyl-CoA.
The four steps are:
- Dehydrogenation (oxidation)
- Hydration
- Dehydrogenation (second oxidation)
- Thiolysis (cleavage)
Reaction Sequence of Beta Oxidation
Each turn of the beta oxidation cycle shortens the fatty acid chain by two carbons and produces one molecule each of FADH₂ and NADH.
Step 1: Dehydrogenation of Acyl-CoA
This is the first oxidation step, catalyzed by the enzyme acyl-CoA dehydrogenase, which contains FAD as a cofactor. The enzyme introduces a double bond between the α and β carbon atoms, converting the molecule into trans-Δ²-enoyl-CoA. FAD is reduced to FADH₂ in this step.
In mitochondria, there are specific acyl-CoA dehydrogenases for short-, medium-, and long-chain fatty acids.
Step 2: Hydration of Enoyl-CoA
The enzyme enoyl-CoA hydratase adds a molecule of water across the double bond, forming L-β-hydroxyacyl-CoA. This enzyme is stereospecific and forms only the L-isomer.
Step 3: Second Dehydrogenation
In this step, β-hydroxyacyl-CoA dehydrogenase catalyzes the oxidation of L-β-hydroxyacyl-CoA to β-ketoacyl-CoA. The coenzyme NAD⁺ acts as the electron acceptor and is reduced to NADH + H⁺.
Step 4: Thiolytic Cleavage
The final step of each cycle is catalyzed by β-ketoacyl-CoA thiolase, which cleaves the bond between the α and β carbons. This reaction releases one molecule of acetyl-CoA and an acyl-CoA chain that is shorter by two carbons.
The shortened acyl-CoA molecule then re-enters the beta oxidation cycle and continues to be degraded until the entire fatty acid is converted into acetyl-CoA units.
Energy Yield of Beta Oxidation
Let’s consider the oxidation of a common saturated fatty acid, stearic acid (C₁₈).
Stearic acid undergoes 8 cycles of beta oxidation to produce 9 molecules of acetyl-CoA, along with 8 FADH₂ and 8 NADH molecules.
Overall Reaction for Stearic Acid Oxidation:
Stearyl–CoA + 8 NAD⁺ + 8 FAD + 8 CoA + 8 H₂O → 9 Acetyl–CoA + 8 FADH₂ + 8 NADH + 8 H⁺
Energy Calculation:
- Each FADH₂ → 2 ATP
- Each NADH → 3 ATP
- Each Acetyl-CoA (in TCA cycle) → 12 ATP
Total ATP from β-oxidation of stearic acid:
- From 8 FADH₂ → 16 ATP
- From 8 NADH → 24 ATP
- From 9 Acetyl-CoA → 108 ATP
- Total = 148 ATP
- Minus 2 ATP used for fatty acid activation → Net yield = 146 ATP
Thus, complete oxidation of one molecule of stearic acid yields 146 ATP in the body.
Efficiency of Beta Oxidation
When stearic acid is oxidized in a calorimeter, it produces approximately 1120 kJ of energy. However, in the body, oxidation yields around 7280 kJ worth of ATP (51.6 kJ per ATP × 146 ATP).
This means that approximately 65% of the total energy from stearic acid oxidation is captured as ATP, while the remaining 35% is lost as heat.
Regulation of Beta Oxidation
Beta oxidation is regulated primarily at the level of fatty acid entry into mitochondria. The key regulatory enzyme is carnitine acyltransferase I (CAT-I).
Role of Malonyl-CoA:
- In fed state: High levels of malonyl-CoA (produced during fatty acid synthesis) inhibit CAT-I, preventing fatty acid oxidation when energy is sufficient.
- During fasting/starvation: Malonyl-CoA levels decrease, relieving inhibition of CAT-I and promoting beta oxidation to generate energy from fat stores.
Thus, beta oxidation is regulated according to the body’s energy demands — active during fasting and suppressed during feeding.
Detailed Notes:
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