β-Oxidation of Saturated Fatty Acid (Palmitic Acid)
Brief on β-Oxidation of Saturated Fatty Acid (Palmitic Acid)
Introduction of β-Oxidation of Saturated Fatty Acid:
Fatty acids play a vital role in cellular metabolism, serving as a major energy source and as precursors for the synthesis of complex lipids.
Among the diverse array of fatty acids, saturated fatty acids like palmitic acid are prominent contributors to energy production in the body.
The breakdown of palmitic acid through β-oxidation represents a fundamental metabolic pathway essential for energy homeostasis and cellular function.
This process occurs predominantly in the mitochondria, where fatty acids are oxidized to generate acetyl-CoA molecules, which subsequently enter the citric acid cycle to produce ATP through oxidative phosphorylation.
The β-oxidation pathway involves a series of enzymatic reactions that sequentially cleave two-carbon units from the acyl chain of palmitic acid, yielding acetyl-CoA molecules and reducing equivalents in the form of FADH₂ and NADH.
This highly regulated process requires the concerted action of specific enzymes and cofactors to ensure efficient fatty acid catabolism while maintaining metabolic balance.
Understanding the mechanisms underlying β-oxidation of saturated fatty acids is crucial for elucidating metabolic disorders, such as fatty acid oxidation disorders, and for developing therapeutic interventions to modulate lipid metabolism.
β-oxidation is the process by which fatty acids are broken down in the mitochondria to generate energy.
Palmitic acid, a saturated fatty acid, undergoes β-oxidation through a series of steps:
Step of β-oxidation:
1. Dehydrogenation:
This step is catalyzed by acyl-CoA dehydrogenase, which removes two hydrogen atoms from the β and γ carbons of the fatty acyl-CoA molecule.
The removal of these hydrogen atoms results in the formation of a trans double bond between these carbons, converting the fatty acyl-CoA into a trans-Δ²-enoyl-CoA.
Acyl-CoA dehydrogenase utilizes FAD (flavin adenine dinucleotide) as a cofactor, which is reduced to FADH₂ during the reaction. FADH₂ serves as an electron carrier and is subsequently oxidized in the electron transport chain to generate ATP.
2. Hydration:
In this step, the trans double bond in the trans-Δ²-enoyl-CoA molecule is hydrated by enoyl-CoA hydratase.
The enzyme adds a water molecule across the double bond, resulting in the formation of a hydroxyl group (-OH) at the β-carbon position of the molecule.
This hydration step converts the trans double bond into a hydroxyl group, yielding a β-hydroxyacyl-CoA intermediate.
3. Dehydrogenation (Second):
Catalyzed by 3-hydroxyacyl-CoA dehydrogenase, this step involves the oxidation of the β-hydroxyacyl-CoA intermediate formed in the previous step.
NAD⁺ (nicotinamide adenine dinucleotide) serves as the electron acceptor, and it is reduced to NADH during the reaction.
The oxidation of the β-hydroxyacyl-CoA results in the formation of a β-ketoacyl-CoA intermediate, with a ketone group at the β-carbon position.
4. Thiolytic Cleavage:
In the final step, catalyzed by β-ketothiolase, the β-ketoacyl-CoA intermediate undergoes thiolytic cleavage.
The enzyme cleaves the bond between the β and α carbons of the β-ketoacyl-CoA, resulting in the release of a molecule of acetyl-CoA from the carboxyl end of the fatty acyl-CoA.
Simultaneously, the remaining portion of the fatty acyl-CoA molecule is attached to CoA, forming a new acyl-CoA molecule that is two carbons shorter than the original fatty acyl-CoA.
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These four steps are repeated iteratively, with each cycle releasing one molecule of acetyl-CoA and shortening the fatty acyl-CoA chain by two carbons until the entire fatty acid molecule is completely oxidized into acetyl-CoA units.
β-oxidation occurs in the mitochondrial matrix and is a crucial pathway for energy production from fatty acids.
This process is repeated until the entire fatty acid chain is broken down into acetyl-CoA units, which can enter the citric acid cycle to generate ATP through oxidative phosphorylation.
End products and energy yield
The end products of β-oxidation (beta oxidation of palmitic acid) of palmitic acid, a 16-carbon saturated fatty acid, are acetyl-CoA molecules. For each round of β-oxidation, a single molecule of palmitic acid yields eight molecules of acetyl-CoA.
These acetyl-CoA molecules can then enter the citric acid cycle (also known as the Krebs cycle or tricarboxylic acid cycle) to undergo further oxidation and ultimately generate ATP through oxidative phosphorylation.
The energy yield from β-oxidation can be calculated based on the number of acetyl-CoA molecules produced and the subsequent ATP generation in the citric acid cycle and oxidative phosphorylation.
Each acetyl-CoA molecule entering the citric acid cycle results in the production of 3 molecules of NADH, 1 molecule of FADH₂, and 1 molecule of GTP (which can be converted to ATP). These reducing equivalents (NADH and FADH₂) then donate electrons to the electron transport chain, where ATP is generated through oxidative phosphorylation.
The overall energy yield from the complete β-oxidation of one molecule of palmitic acid (16 carbons) can be summarized as follows:
β-oxidation produces 8 molecules of acetyl-CoA.
Each acetyl-CoA entering the citric acid cycle yields approximately 12 molecules of ATP through oxidative phosphorylation:
3 ATP from GTP
3 ATP from NADH, and
2 ATP from FADH₂.
Therefore, the total ATP yield from the complete β-oxidation of palmitic acid is approximately 96 ATP molecules (8 acetyl-CoA × 12 ATP/acetyl-CoA).
This makes β-oxidation (beta oxidation of palmitic acid) of fatty acids a highly efficient process for energy production, especially for long-chain fatty acids like palmitic acid, which can yield large amounts of ATP when fully oxidized.