long-chain fatty acid biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of a long-chain fatty acid. A long-chain fatty acid has an aliphatic tail containing 13 to 22 carbons. [PMID:18390550]

Long-chain fatty acid biosynthesis is a fundamental metabolic process that builds fatty acids, essential components of cell membranes, lipids, and other vital molecules. The process occurs primarily in the cytoplasm of eukaryotic cells, with the primary site being the endoplasmic reticulum (ER). Here's a detailed description of the steps involved:

**1. Acetyl-CoA Formation:**

* The process begins with acetyl-CoA, a two-carbon unit derived from the breakdown of carbohydrates (glycolysis) or the oxidation of fatty acids (beta-oxidation).
* Acetyl-CoA enters the mitochondria, where it is converted to citrate.
* Citrate exits the mitochondria and is converted back to acetyl-CoA in the cytoplasm.

**2. Malonyl-CoA Synthesis:**

* Acetyl-CoA is carboxylated to malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC). This step is crucial for the elongation of the fatty acid chain and is the rate-limiting step in fatty acid synthesis.
* ACC requires the cofactor biotin and uses ATP and bicarbonate as substrates.

**3. Fatty Acid Synthase (FAS) Complex:**

* Fatty acid synthesis occurs on a multi-enzyme complex called fatty acid synthase (FAS).
* FAS consists of two identical polypeptide chains, each containing multiple active sites for the different enzymatic reactions.
* In mammals, FAS is a single polypeptide chain, while in bacteria, it is a complex of separate enzymes.

**4. Elongation Cycle:**

* The fatty acid chain is built by repeated addition of two-carbon units from malonyl-CoA.
* Each elongation cycle involves four key reactions:
* **Condensation:** Acetyl-CoA and malonyl-CoA are joined together to form a four-carbon unit.
* **Reduction:** The four-carbon unit is reduced by NADPH.
* **Dehydration:** Water is removed from the four-carbon unit, creating a double bond.
* **Reduction:** The double bond is reduced by NADPH, resulting in a saturated four-carbon unit.

**5. Chain Termination:**

* The elongation cycle continues until the fatty acid chain reaches the desired length (typically 16-18 carbons).
* At this point, the growing chain is released from FAS and is further processed by other enzymes.

**6. Unsaturation:**

* Some fatty acids require desaturation, the introduction of double bonds.
* This process is catalyzed by desaturase enzymes, which utilize molecular oxygen and NADPH.
* Unsaturated fatty acids, such as oleic acid (18:1), linoleic acid (18:2), and linolenic acid (18:3), are essential components of cell membranes and precursors to important signaling molecules.

**7. Regulation of Fatty Acid Biosynthesis:**

* Fatty acid synthesis is tightly regulated to ensure adequate supply of fatty acids while avoiding excessive accumulation.
* Key regulatory mechanisms include:
* **Hormonal control:** Insulin stimulates fatty acid synthesis, while glucagon inhibits it.
* **Substrate availability:** The availability of acetyl-CoA and NADPH influences the rate of synthesis.
* **Product feedback:** Long-chain fatty acids can inhibit the activity of ACC, the rate-limiting enzyme.

**8. Importance of Fatty Acid Biosynthesis:**

* Fatty acids are essential for:
* **Membrane structure:** Forming the phospholipid bilayer of cell membranes.
* **Energy storage:** Triglycerides, the primary energy storage form, are composed of fatty acids.
* **Hormone production:** Steroid hormones, such as testosterone and estrogen, are derived from fatty acids.
* **Signaling molecules:** Eicosanoids, important signaling molecules involved in inflammation and blood clotting, are derived from polyunsaturated fatty acids.

**In summary, the long-chain fatty acid biosynthetic process is a complex and highly regulated pathway that is essential for life. It involves the formation of acetyl-CoA, malonyl-CoA, and the elongation of the fatty acid chain by the FAS complex. The process is tightly controlled by hormones, substrate availability, and product feedback mechanisms. The fatty acids produced are crucial for cell structure, energy storage, hormone production, and signaling.**'"

Proteins (22)

Compounds (1,140)