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.
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