What is lipid biosynthesis

Fatty acid synthesis

Synonym: fatty acid biosynthesis
English: synthesis of fatty acids

1 definition

The term Fatty acid synthesis covers the various steps that lead to the synthesis of a fatty acid in the body. Activated fatty acids are used for the synthesis of triacylglycerides and membrane lipids.

2 Course of the synthesis

2.1 Transport of acetyl-CoA into the cytosol

In preparation for the synthesis, acetyl-CoA has to be transported from the mitochondrion into the cytosol. This takes place via the so-called citrate shuttle. Acetyl-CoA is converted to citrate in the citric acid cycle, which can then pass through the inner mitochondrial wall. In the cytosol, CoA-SH and ATP are required for the release of acetyl-CoA. The resulting oxaloacetate is converted to pyruvate via malate, whereby one NADH is consumed and one NADPH is formed.

2.2 Saturated Fatty Acids

2.2.1 Formation of malonyl-CoA

In a first step, malonyl-CoA must first be synthesized from acetyl-CoA. This carboxylation is catalyzed by the biotin-dependent acetyl-CoA carboxylase.

2.2.2 Condensation

The following synthesis is catalyzed by the dimeric enzyme fatty acid synthase located in the cytosol. With its acyl carrier protein, this has a central and a peripheral sulfhydryl group, also known as a thiol group.

The central group initially takes up the acetyl residue from the acetyl-CoA. This is then transferred to the peripheral thiol group.

The central group can take up the previously formed malonyl-CoA in a next reaction. The acetyl residue is now transferred back to the central group, with condensation taking place with the splitting off of carbon dioxide and the chain being lengthened by two carbon atoms.

The resulting keto group of the acetacetyl residue is then reduced to a secondary alcohol with NADPH. The subsequent dehydration gives an alpha-beta-unsaturated double bond, which is then saturated by reaction with NADPH.

The carboxylic acid formed in these reactions is then transferred back to the peripheral thiol group and can react with another malonyl-CoA in a next reaction.

When synthesizing an odd-numbered fatty acid, propionyl-CoA is required as a substrate instead of acetyl-CoA.

2.3 Unsaturated fatty acids

2.3.1 Activation of a fatty acid

In order to synthesize an unsaturated fatty acid, the saturated fatty acid must first be activated, i.e. it must combine with coenzyme A. This reaction is catalyzed by the thiokinase.

First of all, ATP is split into AMP and pyrophosphate. The pyrophosphate is further split into orthophosphate by a pyrophosphatase. In the following reaction, the fatty acid and the AMP react to form acyl adenylate.

Due to the energy released when AMP is split off, the fatty acid can be esterified with coenzyme A: Acyl-CoA is formed.

2.3.2 Incorporation of a double bond

A double bond can then be incorporated by catalysis of the cytochrome b5-dependent acyl-CoA desaturase, but only between carbon 1 and carbon 9 of a fatty acid. The desaturases are NADPH- and oxygen-dependent.

This reaction mainly takes place in the microsomes of the hepatocytes. In the human metabolism, only one double bond can normally be incorporated into a fatty acid. By lengthening the chain, however, a second double bond can also be incorporated, which is the case, for example, when converting linoleic acid into arachidonic acid.

2.4 Long-chain fatty acids

Fatty acid synthase only enables the formation of short-chain fatty acids, especially those with 14, 16 and 18 carbon atoms. Longer-chain fatty acids are produced by chain extension with the help of elongases. This elongation is possible independently of one another in the endoplasmic reticulum or in the mitochondria.

3 regulation of synthesis

The enzyme acetyl-CoA carboxylase is the regulatory point for the synthesis. NADPH, ATP and citrate activate the enzyme, acyl-CoA inhibits it. Insulin is an inducer, cAMP a repressor. Fatty acids are mainly synthesized when the cell has enough energy and carbohydrates.