Role of Fatty Acid Synthase Complex in Fatty Acid Metabolism
Introduction
The fatty acid synthase (FAS) complex is a multi-enzyme protein responsible for catalyzing the synthesis of long-chain saturated fatty acids from acetyl-CoA and malonyl-CoA precursors. It plays a vital role in lipid metabolism and energy storage, particularly in the liver, adipose tissue, and mammary glands during lactation.
Structure of the Fatty Acid Synthase Complex
In humans and other vertebrates, FAS is a homodimeric enzyme complex where each monomer has several functional domains. These domains work sequentially to elongate fatty acid chains in a cycle of reactions.
Main Functions of Fatty Acid Synthase
1. Initiation Step
- Acetyl-CoA is attached to the acyl carrier protein (ACP) domain of FAS to begin the synthesis process.
2. Chain Elongation
The chain elongation process includes the following steps:
- Condensation: Malonyl-CoA is added, and CO₂ is released, forming a four-carbon molecule.
- Reduction: The molecule is reduced using NADPH to convert keto to hydroxy form.
- Dehydration: Water is removed to create a double bond.
- Second Reduction: The double bond is reduced again with NADPH to a single bond.
This cycle repeats until a 16-carbon saturated fatty acid (palmitic acid) is produced.
3. Termination
- After seven cycles of elongation, the enzyme thioesterase releases the complete fatty acid from the complex.
Regulation of FAS Activity
Fatty acid synthase is regulated both transcriptionally and allosterically:
- Induced by: Insulin and high-carbohydrate diets, especially in the fed state.
- Inhibited by: Fasting, glucagon, and polyunsaturated fatty acids.
Physiological Importance
- Provides fatty acids for energy storage as triglycerides.
- Contributes to membrane lipid synthesis.
- Supports milk fat synthesis in lactating mammals.
Conclusion
The fatty acid synthase complex is essential for de novo synthesis of fatty acids. By integrating precursors like acetyl-CoA and malonyl-CoA, it enables the production of palmitic acid, which is further modified to generate a variety of lipids crucial for cellular and physiological functions.