Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (By similarity). ACSL3 is required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins) (By similarity). 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 (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-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.