Acyl-CoA synthetases, also known as acyl-CoA ligases, are enzymes that "activate" fatty acids by thioesterification to coenzyme A. It represents the initial step of fatty acid metabolism so that fatty acids can participate in catabolic and anabolic pathways. 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.

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.

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

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

In summary:

Members +SymbolNameLocalizationEC numberPreferred substrateProductEnzyme defectPrevalence Short-chain acyl-CoA synthetase familyACSS1Acyl-CoA synthetase short-chain family member 1MitochondrionEC 6.2.1.1 EC 6.2.1.17AcetateAcetyl-CoAACSS2Acyl-CoA synthetase short-chain family member 2CytosolEC 6.2.1.1 EC 6.2.1.17AcetateAcetyl-CoAACSS3Acyl-CoA synthetase short-chain family member 3Mitochondrial matrixEC 6.2.1.1 EC 6.2.1.17PropionatePropionyl-CoA Medium-chain acyl-CoA synthetase family (C6-C10)ACSM1Acyl-CoA synthetase medium-chain family member 1Mitochondrial matrixEC 6.2.1.2 EC 6.2.1.25ACSM2AAcyl-CoA synthetase medium-chain family member 2AMitochondrionEC 6.2.1.2 EC 6.2.1.25Medium chain fatty acidsACSM2BAcyl-CoA synthetase medium-chain family member 2BMitochondrionEC 6.2.1.2 EC 6.2.1.25ACSM3Acyl-CoA synthetase medium-chain family member 3MitochondrionEC 6.2.1.17 EC 6.2.1.2ACSM4Acyl-CoA synthetase medium-chain family member 4MitochondrionEC 6.2.1.2Decanoate-CoA (predicted)ACSM5Acyl-CoA synthetase medium-chain family member 5MitochondrionEC 6.2.1.2ACSM6Acyl-CoA synthetase medium-chain family member 6MitochondrionEC 6.2.1.2 Long-chain acyl-CoA synthetase familyACSL1Acyl-CoA synthetase long-chain family member 1EC 6.2.1.15 EC 6.2.1.24 EC 6.2.1.3Free long-chain fatty acidsFatty acyl-CoA estersACSL3Acyl-CoA synthetase long-chain family member 3EC 6.2.1.15 EC 6.2.1.2 EC 6.2.1.3Myristate, arachidonate, eicosapentaenoate ACSL4Acyl-CoA synthetase long-chain family member 4PeroxisomeEC 6.2.1.15 EC 6.2.1.3ArachidonateIntellectual developmental disorder, X-linked 63ACSL5Acyl-CoA synthetase long-chain family member 5EC 6.2.1.15 EC 6.2.1.3ACSL6Acyl-CoA synthetase long-chain family member 6EC 6.2.1.15 EC 6.2.1.3 Very long-chain acyl-CoA synthetase family (>C22)SLC27A1Solute carrier family 27 (fatty acid transporter), member 1Plasma membraneEC 6.2.1.15 EC 6.2.1.3SLC27A2Solute carrier family 27 (fatty acid transporter), member 2Endoplasmic reticulum, peroxisomeEC 6.2.1.15 EC 6.2.1.24 EC 6.2.1.3 EC 6.2.1.7Long-chain, branched-chain and very long-chain fatty acidsFatty acyl-CoA estersSLC27A3Solute carrier family 27 (fatty acid transporter), member 3EC 6.2.1.15 EC 6.2.1.3SLC27A4Solute carrier family 27 (fatty acid transporter), member 4PeroxisomeEC 6.2.1.15 EC 6.2.1.3Ichthyosis prematurity syndromeSLC27A5Solute carrier family 27 (fatty acid transporter), member 5Endoplasmic reticulumEC 6.2.1.3 EC 6.2.1.7Very long-chain fatty-acids containing 24- and 26-carbonsSLC27A6Solute carrier family 27 (fatty acid transporter), member 6EC 6.2.1.15 EC 6.2.1.3 Bubblegum acyl-CoA synthetase familyACSBG1Acyl-CoA synthetase bubblegum family member 1EC 6.2.1.3ACSBG2Acyl-CoA synthetase bubblegum family member 2Cytosol, MitochondrionEC 6.2.1.15 EC 6.2.1.3 Other acyl-CoA synthetases AACSAcetoacetyl-CoA synthetaseCytosol (predicted)EC 6.2.1.16AcetoacetateAcetoacetyl-CoA (predicted)ACSF2Acyl-CoA synthetase family member 2MitochondrionEC 6.2.1.2ACSF3Acyl-CoA synthetase family member 3MitochondrionEC 6.2.1.76Malonate, methylmalonate, lignocerateMalonyl-CoA, methylmalonyl-CoACombined malonic and methylmalonic aciduria (CMAMMA)1: 30,000AASDHAminoadipate-semialdehyde dehydrogenaseEC 6.2.1.-

See also

Acyl-CoA Long-chain acyl-CoA synthetase

References