Beta-oxidation Steps (β-Oxidation)

What is β-Oxidation step in Fatty Acid?

β-Oxidation is a metabolic process that occurs in the mitochondria of cells and plays a crucial role in the breakdown of fatty acids.

  • It is a multi-step process that involves the sequential removal of two-carbon units from the fatty acid chain, resulting in the production of acetyl-CoA.
  • Acetyl-CoA can then enter the citric acid cycle to generate energy.
  • The process of beta-oxidation(β-Oxidation) can be divided into four main steps: activation, translocation, oxidation, and cleavage.
  • Each step involves specific enzymes and reactions that work together to break down the fatty acid molecule.
β-Oxidation step
β-Oxidation step (Source: wikipedia)

Step 1: Activation of β-Oxidation

  • The first step in beta-oxidation (β Oxidation)is the activation of the fatty acid molecule. This step occurs in the cytoplasm and involves the conversion of the fatty acid to its acyl-CoA derivative.
  • The reaction is catalyzed by an enzyme called acyl-CoA synthetase or fatty acyl-CoA synthetase.
  • The acyl-CoA synthetase enzyme requires ATP and CoA to convert the fatty acid to its acyl-CoA form. The reaction proceeds as follows:

Fatty acid + ATP + CoA → Fatty acyl-CoA + AMP + PPi

  • The acyl-CoA molecule is now ready to enter the mitochondria for further processing.

Step 2: Translocation

  • Once the fatty acyl-CoA molecule is formed, it needs to be transported into the mitochondria, where beta-oxidation takes place.
  • The translocation of the fatty acyl-CoA across the mitochondrial membrane is facilitated by a carnitine shuttle system. The shuttle system involves several enzymes and transporters, including carnitine palmitoyltransferase I (CPT-I), carnitine acylcarnitine translocase, and carnitine palmitoyltransferase II (CPT-II).
  • First, CPT-I, located on the outer mitochondrial membrane, catalyzes the transfer of the acyl group from CoA to carnitine, forming acylcarnitine.
  • The CoA is released back into the cytoplasm. Acylcarnitine is then transported across the mitochondrial membrane by the carnitine acylcarnitine translocase.
  • Once inside the mitochondria, CPT-II, located on the inner mitochondrial membrane, catalyzes the transfer of the acyl group from carnitine back to CoA.
  • The carnitine is released back into the cytoplasm, and the fatty acyl-CoA is now available for further processing.

Step 3: Oxidation in β-Oxidation

  • The oxidation step is the key step in beta-oxidation, where the fatty acyl-CoA molecule is sequentially oxidized to produce acetyl-CoA units. This step involves a series of reactions that occur in the mitochondrial matrix.
  • The reactions are catalyzed by four enzymes, namely acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and thiolase. Each enzyme acts on a specific intermediate of the beta-oxidation cycle.
  • The first enzyme, acyl-CoA dehydrogenase, catalyzes the removal of two hydrogen atoms from the beta-carbon of the acyl-CoA molecule, resulting in the formation of a trans-enoyl-CoA intermediate.
  • There are several isoforms of acyl-CoA dehydrogenase, each specific to different chain lengths of fatty acids.
  • The second enzyme, enoyl-CoA hydratase, catalyzes the addition of water across the double bond in the trans-enoyl-CoA molecule, leading to the formation of a beta-hydroxyacyl-CoA intermediate.
  • The third enzyme, 3-hydroxyacyl-CoA dehydrogenase, oxidizes the beta-hydroxyacyl-CoA molecule, removing two hydrogen atoms and forming a ketoacyl-CoA intermediate.
  • The final enzyme, thiolase, catalyzes the cleavage of the ketoacyl-CoA molecule, resulting in the release of an acetyl-CoA molecule and the formation of a new fatty acyl-CoA molecule, which is two carbons shorter than the original fatty acyl-CoA.
  • This cycle is repeated for each two-carbon unit in the fatty acid chain, resulting in the successive removal of acetyl-CoA units. The process continues until the entire fatty acid molecule is completely oxidized

Step 4: Cleavage in β-Oxidation

  • At the end of the beta-oxidation process, the fatty acid chain is completely broken down into acetyl-CoA units.
  • The acetyl-CoA can then enter the citric acid cycle to generate energy through oxidative phosphorylation. The number of acetyl-CoA units generated depends on the length of the original fatty acid chain.
  • For example, if the original fatty acid chain is palmitic acid (a 16-carbon fatty acid), the beta-oxidation process will produce eight acetyl-CoA units.
  • Each acetyl-CoA unit can enter the citric acid cycle, generating ATP through the subsequent steps of oxidative phosphorylation.
  • In summary, beta-oxidation is a complex metabolic process that involves the sequential breakdown of fatty acids into acetyl-CoA units.
  • The process occurs in four steps: activation, translocation, oxidation, and cleavage. Each step involves specific enzymes and reactions that work together to efficiently break down fatty acids and produce energy.
  • Understanding the steps and mechanisms of beta-oxidation is essential for studying lipid metabolism and energy production in cells.

β-Oxidation of saturated fatty acid (Palmitic acid)

  • Beta-oxidation is a metabolic pathway that breaks down fatty acids into acetyl-CoA molecules, which can be further utilized by the cell for energy production. Let’s explore the detailed process of beta-oxidation specifically for the saturated fatty acid palmitic acid, which contains 16 carbon atoms.
  • Step 1: Activation
    • Palmitic acid, located in the cytoplasm, undergoes activation to form palmitoyl-CoA, which is the acyl-CoA derivative of palmitic acid. This step requires ATP and is catalyzed by an enzyme called acyl-CoA synthetase or fatty acyl-CoA synthetase. The reaction can be represented as follows:

Palmitic acid + ATP + CoA → Palmitoyl-CoA + AMP + PPi

  • The resulting palmitoyl-CoA is now ready for translocation into the mitochondria, where beta-oxidation will occur.
  • Step 2: Translocation
    • Palmitoyl-CoA is transported across the mitochondrial membrane via the carnitine shuttle system. The process involves several enzymes and transporters, including carnitine palmitoyltransferase I (CPT-I), carnitine acylcarnitine translocase, and carnitine palmitoyltransferase II (CPT-II).
    • First, CPT-I, located on the outer mitochondrial membrane, catalyzes the transfer of the acyl group from CoA to carnitine, forming palmitoylcarnitine.
    • This reaction requires the presence of malonyl-CoA, which acts as an inhibitor of CPT-I, ensuring that fatty acid oxidation and fatty acid synthesis do not occur simultaneously.
    • The CoA is released back into the cytoplasm.
    • Palmitoylcarnitine is then transported across the mitochondrial membrane by the carnitine acylcarnitine translocase.
    • Inside the mitochondrial matrix, CPT-II, located on the inner mitochondrial membrane, catalyzes the transfer of the acyl group from carnitine back to CoA. The carnitine is released back into the cytoplasm, and the palmitoyl-CoA is now available for beta-oxidation.
  • Step 3: Oxidation
    • The oxidation of palmitoyl-CoA occurs via a series of reactions, each catalyzed by specific enzymes. Let’s go through the four major reactions involved in the beta-oxidation of palmitic acid:
  1. Reaction 1: Oxidation
    • The first reaction is catalyzed by acyl-CoA dehydrogenase, which comes in different isoforms based on the chain length of the fatty acid. For palmitoyl-CoA, the enzyme specific to long-chain fatty acids, called long-chain acyl-CoA dehydrogenase (LCAD), is involved. LCAD removes two hydrogen atoms from the beta-carbon of palmitoyl-CoA, resulting in the formation of trans-delta^2-enoyl-CoA and FADH2 (flavin adenine dinucleotide, an electron carrier). The reaction can be summarized as follows:

Palmitoyl-CoA + FAD → trans-delta^2-enoyl-CoA + FADH2

  • Reaction 2: Hydration
    • The second reaction is catalyzed by enoyl-CoA hydratase, also known as 2-enoyl-CoA hydratase. This enzyme adds water to the trans-delta^2-enoyl-CoA molecule, resulting in the formation of L-3-hydroxyacyl-CoA. The reaction can be represented as follows:

trans-delta^2-enoyl-CoA + H2O → L-3-hydroxyacyl-CoA

  • Reaction 3: Oxidation
    • The third reaction involves the oxidation of L-3-hydroxyacyl-CoA. This step is facilitated by an enzyme called L-3-hydroxyacyl-CoA dehydrogenase.
    • The enzyme oxidizes L-3-hydroxyacyl-CoA, removing two hydrogen atoms and generating NADH (nicotinamide adenine dinucleotide, another electron carrier).
    • The resulting product is 3-ketoacyl-CoA. The reaction can be represented as follows:

L-3-hydroxyacyl-CoA + NAD+ → 3-ketoacyl-CoA + NADH + H+

  • Reaction 4: Thiolysis
    • The final reaction, catalyzed by thiolase, involves the cleavage of the 3-ketoacyl-CoA molecule. Thiolase breaks the molecule between the alpha and beta carbons, resulting in the formation of an acetyl-CoA molecule and a new fatty acyl-CoA molecule, which is two carbons shorter than the original palmitoyl-CoA. The reaction can be summarized as follows:

3-ketoacyl-CoA + CoA → Acetyl-CoA + Fatty acyl-CoA (two carbons shorter)

  • The new fatty acyl-CoA produced can re-enter the beta-oxidation cycle, repeating the oxidation steps until the entire palmitic acid molecule is completely broken down into acetyl-CoA units.
  • Step 4: Iteration and Cleavage
    • The beta-oxidation cycle continues with the newly formed fatty acyl-CoA, repeating the oxidation steps until all the carbon atoms are cleaved into acetyl-CoA units. For palmitic acid, which contains 16 carbon atoms, the process goes through seven iterations of the oxidation steps.
  • The final acetyl-CoA units generated from each iteration can enter the citric acid cycle (also known as the Krebs cycle or TCA cycle) within the mitochondria. In the citric acid cycle, acetyl-CoA is further metabolized, generating energy in the form of ATP through oxidative phosphorylation.

  • In summary, the beta-oxidation of palmitic acid, a saturated fatty acid with 16 carbon atoms, involves the activation of palmitic acid to palmitoyl-CoA, followed by translocation into the mitochondria.
  • Once inside, the oxidation steps occur, which include three reactions (oxidation, hydration, and oxidation) and a final cleavage reaction.
  • This process is iterated multiple times until the entire fatty acid chain is broken down into acetyl-CoA units. The acetyl-CoA units can then be utilized for energy production in the citric acid cycle.

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