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 (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:
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:
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:
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:
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:
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.