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What is Fatty Acid Synthase?

By Helga George
Updated May 17, 2024
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Fatty acids have an acidic group on one end, connected to a hydrocarbon chain that repels water. They are very important cellular components, serving structural roles as membrane components, signaling roles as hormones, and as energy sources to fuel metabolism. Humans obtain many types of fatty acids from their diets, but several types must be synthesized by the body. Fatty acid synthesis is mediated in mammals by a large pair of proteins containing a number of different enzymes that work together, and are known as fatty acid synthase (FAS).

This enzymatic system is highly complex and carries out a number of different biochemical reactions, all leading to the synthesis of a fatty acid. The basic reaction of fatty acid synthesis is to combine molecules composed of two carbon units into longer chains to form fatty acids. The fatty acid formed by mammals is the 16-carbon-long compound palmitic acid, also known as C16. Palmitic acid is a saturated fatty acid, meaning it does not contain any double bonds. The biosynthesis of this compound takes place in the cytosol, and there is no association with membranes.

The synthesis of palmitic acid requires more than just the two carbon fatty acid precursors and fatty acid synthase. It also requires a cofactor, which is a non-protein component loosely associated with an enzyme. The cofactor CoA is a sulfur-containing compound that accompanies each of the chemicals that serve as carbon sources for the fatty acid chain. The source of the two carbon units to add to the growing fatty acid chain is the three-carbon cofactor malonyl-CoA, which is produced from the two-carbon compound acetyl-CoA.

Fatty acid synthase must first be activated by contact with acetyl-CoA. After this reaction, FAS sequentially lengthens the nascent fatty acid chain using carbon groups donated from malonyl-CoA. This process requires a series of different chemical reactions. As the chain grows, it is passed from one enzyme to the next, until it has reached its final length of 16 carbons. Then it is released from the protein.

There are two types of fatty acid synthase. FAS Type I is the mammalian type that only produces palmitic acid by using a large pair of proteins with each containing several different enzymes. In contrast, FAS Type II is used by bacteria and plants. This multi-enzyme complex has individual enzymes as separate proteins that cluster together. A Type II complex can make additional types of fatty acids, but is not as efficient as the mammalian Type I FAS.

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