Lesson 22 : Fatty Acid Synthesis


Much like ?-oxidation, elongation occurs via four recurring reactions shown below. In these diagrams, the acetyl and malonyl units are shown as their Acyl carrier protein (ACP) thioesters: this is how fatty acids are synthesized in microorganisms and plants.

However, in animals these same reactions occur on a large dimeric protein, Fatty acid synthase, which has the full complement of enzymatic activities required to synthesize and liberate a free fatty acid.






The first step is condensation of acetyl CE and malonyl ACP. This results in the formation of acetoacetyl ACP. Although this reaction is thermodynamically unfavourable, the evolution of CO2 drives the reaction forward.

?-Ketoacyl-ACP synthase

Reduction of acetoacetyl ACP

In this step, acetoacetyl ACP is reduced by NADPH into D-3-Hydroxybutyryl ACP. The double bond is reduced to a hydroxyl group. Only the D isomer is formed.

?-Ketoacyl ACP reductase


In this reaction, D-3-Hydroxybutyryl ACP is dehydrated to crotonyl ACP.

3-Hydroxyacyl ACP dehydrase

Reduction of crotonyl ACP

During this final step, crotonyl ACP is reduced by NADPH into butyryl ACP.

Enoyl ACP reductase

Butyryl CoA is then translocated in the CE site, and another malonyl CoA is brought in the ACP site. In the second step of elongation, butyryl-CE condenses with malonyl ACP to form an acyl ACP compound. This continues until a C16 acyl compound is formed, at which point it is hydrolyzed by a thioesterase into palmitate and ACP.

The end-product of these reactions is always palmitate. No intermediates are released until palmitate is formed. After release from the ACP, palmitate is esterified to Coenzyme A, as this is done with all free fatty acids inside cells to prevent lysis of the cell membranes. If further elongation has to happen, the palmitoyl CoA, or any other acyl-CoA from a dietary acid, then moves into the endoplasmic reticulum, where it can be elongated up to a length of 20 to 24 carbons by essentially the same chain of reactions as happens in the cytosolic ACP. The need of lipogenesis is to store the glucose that remains after the glycostic & gluconeogenesis pathways

Desaturases introduce double bonds at specific positions in a fatty acid chain. Mammalian cells are unable to produce double bonds at certain locations, e.g., Thus some polyunsaturated fatty acids are dietary essentials, e.g., linoleic acid, 18:2 cis (18 carbon atoms long, with cis double bonds at carbons 9-10 & 12-13). Formation of a double bond in a fatty acid involves enzymes like NADH-cyt b5 Reductase, Cytochrome b5, and Desaturase,

There is a 4-electron reduction of O2 to form 2 H2O as a fatty acid is oxidized to form a double bond. Two electrons are extracted from the fatty acid as the double bond is formed.

For example the overall reaction for desaturation of stearate (18:0) to form oleate (18:1 cis D9) is:


Last modified: Monday, 19 March 2012, 9:29 AM