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AAT Bioquest

What is the process of fatty acid synthesis?

Posted October 23, 2023


Answer

Fatty acid synthesis is a multi-step process that occurs in the cytoplasm and ER of the cell. The accumulation of acetyl-CoA in the mitochondria triggers its initial transport into the cytoplasm via citrate and acetylcarnitine. One acetyl-CoA molecule is then converted to malonyl-CoA through carboxylation catalyzed by ACC. There is also one molecule of acetyl-CoA produced in the process that is not converted to malonyl-CoA. Both of these molecules then have their acetyl groups replaced by the acyl-carrier protein to produce acetyl-ACP and malonyl-ACP. The COO group of malonyl ACP is released as CO2 and the acetyl group (C15 and C16) translocates to the alpha carbon of malonyl ACP, producing 3-keto acyl ACP. This ketone then is reduced to a hydroxyl group using NADPH. Water is then removed in a dehydration reaction from carbons 2 and 3 of the hydroxyl group to generate a trans doubled bonded molecule. A second reduction is then carried out to remove the double bond, producing a saturated molecule. Both reduction reactions require NADPH as a cofactor. This process yields a total of four carbon chains, and a new malonyl-ACP group is then added to the growing chain to repeat the same reactions. For each new cycle, the acyl group transferred to the alpha carbon of malonyl CoA is 2 carbons longer than the previous cycle. This process continues until 16 carbons of palmitoyl-CoA are generated. Lastly, carbon 16 is hydrolyzed from ACP, producing free palmitate.  

Additional resources

Fatty acid synthesis

Screen Quest™ Fluorimetric Fatty Acid Uptake Assay Kit