Mitochondrial acyl-coenzyme A synthetase ACSM3 (aka protein SAH homolog) is expressed in the mitochondrial matrix and possesses medium-chain fatty acid:CoA ligase activity. Based on characterisation experiments in mice, ACSM3 preferentially ligates C2-C6 fatty acids, especially butyrate (BUT, a C4 fatty acid) (Fujino et al. 2001). The product, butyryl-CoA (BT-CoA) is used in beta oxidation. ACSM3 gene variants may be associated with obesity-related hypertension (Iwai et al. 1994, 2002, Telgmann et al. 2007, Tikhonoff et al. 2008). The mechanisms by which ACSM3 gene variants affect blood pressure remain to be elucidated.
Mitochondrial acyl-coenzyme A synthetase ACSM6 is proposed to be located in the mitochondrial matrix and possess the same medium-chain fatty acid:CoA ligase activity as ACSM3.