Beta oxidation

Beta oxidation is the primary metabolic pathway for the degradation of fatty acids. Through this process, long-chain fatty acids are broken down into two-carbon units of Acetyl-CoA, which then enter the Citric Acid Cycle to produce energy.

1. Location and Importance

  • Site: The process occurs within the mitochondrial matrix.

  • Significance: It is a major source of energy for the heart and skeletal muscle during fasting or endurance exercise.

  • Pre-requisite: Long-chain fatty acids must be activated in the cytosol and transported across the inner mitochondrial membrane via the carnitine shuttle.

2. Activation and Transport

Before the cycles begin, fatty acids undergo activation and relocation:

  1. Activation: The enzyme Acyl-CoA synthetase converts the fatty acid into Fatty Acyl-CoA.

    • Reaction: \text{Fatty Acid} + \text{CoA} + ATP \rightarrow \text{Fatty Acyl-CoA} + AMP + PP_i

    • This step consumes the equivalent of 2 high-energy phosphate bonds (2 ATP).

  2. The Carnitine Shuttle: Fatty Acyl-CoA is converted to Acyl-carnitine by CPT-I, transported into the matrix by a translocase, and converted back to Acyl-CoA by CPT-II.

3. The Four Stages of Beta Oxidation

Each cycle consists of four repeating steps that shorten the chain by two carbons (releasing one Acetyl-CoA):

  1. Oxidation (Dehydrogenation):

    • Enzyme: Acyl-CoA dehydrogenase.

    • Process: Removal of hydrogen atoms from the \alpha and \beta carbons to form a trans-double bond.

    • Electron Acceptor: FAD is reduced to FADH_2.

  2. Hydration:

    • Enzyme: Enoyl-CoA hydratase.

    • Process: Water is added across the double bond, creating a hydroxyl group on the \beta carbon (L-3-hydroxyacyl-CoA).

  3. Oxidation:

    • Enzyme: 3-hydroxyacyl-CoA dehydrogenase.

    • Process: The hydroxyl group is oxidized to a ketone group.

    • Electron Acceptor: NAD^+ is reduced to NADH + H^+.

  4. Thiolysis:

    • Enzyme: \beta-ketothiolase (Thiolase).

    • Process: Coenzyme A (\text{CoA-SH}) attacks the \beta-keto group, splitting the molecule into one Acetyl-CoA and a new Fatty Acyl-CoA that is two carbons shorter.

4. Energy Yield Calculation

To calculate the ATP yield for a saturated even-chain fatty acid with n carbons:

  • Number of Acetyl-CoA Produced: n/2

  • Number of Cycles: (n/2) - 1

  • Example (Palmitate, C_{16}):

    • 7 cycles produce 7 FADH_2 and 7 NADH.

    • 8 \text{ Acetyl-CoA} molecules are produced.

    • Total ATP Yield: 8 \times 10 \text{ (from Citric Cycle)} + 7 \times 1.5 \text{ (from } FADH_2) + 7 \times 2.5 \text{ (from } NADH) = 108 \text{ ATP}.

    • Net Yield: 108 - 2 \text{ (activation cost)} = 106 \text{ ATP}.