Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:28209804, PubMed:19737935, PubMed:15683247). 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 (PubMed:19737935). Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates (PubMed:9276691, PubMed:8663269). Both isoforms exhibit the same level of activity (PubMed:9276691). 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 a medium chain fatty acid + ATP + CoA = a medium-chain fatty acyl-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 (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-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 Predominantly expressed in the brain, and to a much lesser extent, in lung, adrenal gland, kidney, small intestine, and adipose tissue but not detected in heart or liver. Detected 5 days after birth, increased to a maximal level at 15 days, and then decreased gradually to 10% of its maximum level in adult. 5 rat isozymes encoded by different genes have been described. ACSL6 corresponds to isozyme 2 (ACS2). Belongs to the ATP-dependent AMP-binding enzyme family.