Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490). Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins) (PubMed:18003621). Has mainly an anabolic role in energy metabolism. Mediates hepatic lipogenesis. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates. Both isoforms exhibit the same level of activity (By similarity). a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate a medium chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate ATP + CoA + hexadecanoate = AMP + diphosphate + hexadecanoyl-CoA ATP + CoA + tetradecanoate = AMP + diphosphate + tetradecanoyl-CoA ATP + CoA + dodecanoate = AMP + diphosphate + dodecanoyl-CoA ATP + CoA + octadecanoate = AMP + diphosphate + octadecanoyl-CoA ATP + CoA + eicosanoate = AMP + diphosphate + eicosanoyl-CoA (9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate (9Z)-hexadecenoate + ATP + CoA = (9Z)-hexadecenoyl-CoA + AMP + diphosphate (9Z,12Z)-octadecadienoate + ATP + CoA = (9Z,12Z)-octadecadienoyl-CoA + AMP + diphosphate (9Z,12Z,15Z)-octadecatrienoate + ATP + CoA = (9Z,12Z,15Z)-octadecatrienoyl-CoA + AMP + diphosphate (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + ATP + CoA = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + AMP + diphosphate a fatty acid + ATP + CoA = a fatty acyl-CoA + AMP + diphosphate Belongs to the ATP-dependent AMP-binding enzyme family.