Fatty acyl CoA synthetase from Antarctic notothenioid fishes may influence substrate specificity of fat oxidation

Abstract Antarctic notothenioid fishes possess large lipid stores that are important fuels for aerobic metabolism. Oxidative muscle tissues of these animals oxidize long-chain mono-unsaturated fatty acids more readily than saturated fatty acids. The mechanistic basis(es) for the substrate specificity of their fatty acid-oxidizing pathway is unknown. We examined the substrate specificity of fatty acyl coenzyme A synthetase (FACS) to determine whether the enzyme contributes to targeting unsaturated fatty acids for preferential transport into mitochondria as fuels for β-oxidation. Maximal activities of FACS were measured in isolated mitochondria from Notothenia coriiceps and Chaenocephalus aceratus oxidative skeletal muscles in the presence of fatty acids differing in chain lengths and degrees of unsaturation. With the exception of C 22:6 , maximal activities were greater with unsaturated substrates than with C 16:0 , a saturated fatty acid. Monoenoic fatty acids did not produce the highest activities. Predicted amino acid sequences of FACS from Antarctic C. aceratus , Gobionotothen gibberifrons, and N. coriiceps and sub-Antarctic Notothenia angustata and Eleginops maclovinus were determined to identify amino acid candidates that may be important for determining the substrate specificity of FACS. Substitutions cysteine 548 and polar threonine 552 within the putative fatty acid binding pocket may contribute to preference for unsaturated fatty acyl substrates compared to saturated fatty acids.