Acyl-CoA synthetase

Acyl-CoA synthetases, also known as acyl-CoA ligases, are enzymes that "activate" fatty acids by thioesterification to coenzyme A.^[1] It represents the initial step of fatty acid metabolism so that fatty acids can participate in catabolic and anabolic pathways.^[1] Among these are, for example, the synthesis of triacylglycerol, phospholipids, plasmalogens, sphingolipids, the degradation of fatty acids for energy production, the conversion to alcohols or aldehydes, the elongation of fatty acids, the insertion and removal of double bonds or the covalent binding to proteins.^[1][2]

The members of this family mainly activate fatty acids, but there are also members that activate other substrates instead, such as AACS, which activates the keto acid acetoacetic acid, or ACSF3, which activates the dicarboxylic acids methylmalonic acid and malonic acid.^[3][4]

Reaction

Acyl-CoA synthetases catalyze fatty acid activation, which consists of 2 steps.^[1] First, an ATP-dependent adenylation and release of pyrophophates takes place:^[1]

${\displaystyle \mathrm {Fatt{y}\ acid+ATP\ \xrightarrow {\ } Acyl{-}AMP+PP_{i}} }$

In the 2nd step, CoA-SH displaces the adenylate group, which is released as AMP, and forms a thioester bond with the substrate.^[1]

${\displaystyle \mathrm {Acyl{-}AMP+CoA{-}SH\ \xrightarrow {\ } Acyl{-S-}CoA+AMP} }$

In summary:

${\displaystyle \mathrm {Fatt{y}\ acid+CoA+ATP\ \xrightarrow {\ } Acyl{-}CoA+AMP+PP_{i}} }$

Members

See also

• Acyl-CoA
• Long-chain acyl-CoA synthetase