long-chain fatty acid metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving a long-chain fatty acid. A long-chain fatty acid has an aliphatic tail containing 13 to 22 carbons. [GOC:ajp]

Long-chain fatty acid metabolic process is a fundamental biological process that involves the breakdown and synthesis of long-chain fatty acids, which are fatty acids containing 14 or more carbon atoms. These processes are essential for energy production, membrane formation, and a wide range of other cellular functions.

**Breakdown of Long-Chain Fatty Acids (β-Oxidation)**

1. **Activation:** Long-chain fatty acids are first activated by attaching them to coenzyme A (CoA) in a reaction catalyzed by acyl-CoA synthetase. This process consumes ATP.
2. **Transport into Mitochondria:** Activated fatty acids are transported into the mitochondria, the powerhouse of the cell, via the carnitine shuttle system. This system involves the exchange of fatty acyl-CoA with carnitine, a small molecule, across the mitochondrial membrane.
3. **β-Oxidation Cycle:** The activated fatty acids are then broken down through a series of four enzymatic reactions known as the β-oxidation cycle.
* **Dehydrogenation:** The first reaction removes two hydrogen atoms from the α- and β-carbons of the fatty acyl-CoA, producing a trans-double bond, and reducing FAD to FADH2. This step is catalyzed by acyl-CoA dehydrogenase.
* **Hydration:** Water is added across the double bond, introducing a hydroxyl group at the β-carbon. This reaction is catalyzed by enoyl-CoA hydratase.
* **Dehydrogenation (Again):** The hydroxyl group at the β-carbon is oxidized to a keto group, reducing NAD+ to NADH. This step is catalyzed by β-hydroxyacyl-CoA dehydrogenase.
* **Cleavage:** The β-ketoacyl-CoA is cleaved by β-ketothiolase, releasing a molecule of acetyl-CoA and a new fatty acyl-CoA molecule that is two carbons shorter than the original.
4. **Repeat:** The shortened fatty acyl-CoA molecule cycles through the β-oxidation pathway until it is completely broken down into acetyl-CoA molecules.

**Synthesis of Long-Chain Fatty Acids (Fatty Acid Synthesis)**

1. **Acetyl-CoA Transport:** Acetyl-CoA units from glycolysis or β-oxidation are transported from the mitochondria into the cytoplasm.
2. **Malonyl-CoA Formation:** Acetyl-CoA is carboxylated to malonyl-CoA by acetyl-CoA carboxylase. This is the committed step in fatty acid synthesis.
3. **Fatty Acid Synthase Complex:** The synthesis of long-chain fatty acids occurs on a multi-enzyme complex called fatty acid synthase. This complex is responsible for the cyclical addition of two-carbon units to a growing fatty acid chain.
4. **Chain Elongation:** Each cycle of fatty acid synthesis involves four enzymatic reactions:
* **Condensation:** Acetyl-CoA and malonyl-CoA are condensed to form acetoacetyl-CoA.
* **Reduction:** Acetoacetyl-CoA is reduced to β-hydroxybutyryl-CoA by NADPH.
* **Dehydration:** β-hydroxybutyryl-CoA is dehydrated to crotonyl-CoA.
* **Reduction (Again):** Crotonyl-CoA is reduced to butyryl-CoA by NADPH.
5. **Chain Termination:** The process continues until the fatty acid chain reaches the desired length. The final step involves the release of the fatty acid from the fatty acid synthase complex.

**Regulation of Fatty Acid Metabolism**

The breakdown and synthesis of long-chain fatty acids are tightly regulated to meet the energy needs of the cell and maintain appropriate levels of fatty acids in the body. Key regulatory mechanisms include:

* **Insulin and Glucagon:** These hormones regulate the activity of key enzymes involved in fatty acid metabolism, such as acetyl-CoA carboxylase and carnitine palmitoyltransferase.
* **Citrate:** Citrate is a product of the citric acid cycle and inhibits acetyl-CoA carboxylase, reducing fatty acid synthesis.
* **Malonyl-CoA:** Malonyl-CoA is an intermediate in fatty acid synthesis and inhibits carnitine palmitoyltransferase, reducing β-oxidation.

**Biological Significance**

Long-chain fatty acid metabolism is essential for:

* **Energy Production:** Fatty acids are a major source of energy for the body.
* **Membrane Formation:** Fatty acids are a key component of cell membranes, providing structural integrity and regulating membrane fluidity.
* **Signal Transduction:** Fatty acids can act as signaling molecules, regulating various cellular processes.
* **Hormone Synthesis:** Some fatty acids are precursors for the synthesis of hormones, such as steroid hormones.

**Disorders of Fatty Acid Metabolism**

Defects in enzymes involved in long-chain fatty acid metabolism can lead to various genetic disorders, including:

* **Carnitine Deficiency:** Deficiency in carnitine can impair the transport of fatty acids into the mitochondria, leading to energy deficiency and accumulation of fatty acids in the blood.
* **Fatty Acid Oxidation Disorders:** Defects in enzymes involved in β-oxidation can lead to the accumulation of toxic fatty acid intermediates, causing damage to tissues and organs.
* **Fatty Acid Synthesis Disorders:** Defects in enzymes involved in fatty acid synthesis can lead to impaired growth and development.

In conclusion, long-chain fatty acid metabolic process is a vital and complex biological process that plays a crucial role in cellular energy production, membrane formation, and other essential functions. This process is tightly regulated by various mechanisms to maintain cellular homeostasis and support the overall well-being of the organism.'
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Proteins (8)

Compounds (481)