Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:8978480, PubMed:10198260, PubMed:10749848, PubMed:28209804). Preferentially uses palmitoleate, oleate and linoleate (By similarity). Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs) (PubMed:28209804). 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 3,7,11,15-tetramethylhexadecanoate + ATP + CoA = AMP + diphosphate + phytanoyl-CoA ATP + CoA + hexadecanoate = AMP + diphosphate + hexadecanoyl-CoA (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate 2,6,10,14-tetramethylpentadecanoate + ATP + CoA = AMP + diphosphate + pristanoyl-CoA 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate (9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate Inhibited at high temperature and by arachidonate. Liver, heart, epididymal adipose and to a lesser extent brain, small intestine and lung. Levels remain constant during development. By high fat and high carbohydrate diets. 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.