Activation of free fatty acids in subcellular fractions of human skeletal muscle.

In human pathology little is known about the activating enzymes for fatty acids of different carbon chain length. In order to have a better insight into disorders of lipid metabolism in human skeletal muscle, we studied the distribution of acyl-CoA synthetases in muscular subcellular fractions. We find that in muscle mainly long chain fatty acids are activated to CoA esters. Distribution of palmityl-CoA synthetase in subcellular fractions compared with marker enzymes suggested that this enzymatic activity is located only in the outer mitochondrial membrane, in contrast to human liver, where this enzyme is also located in the microsomes. In human skeletal muscle we also found low butyryl-CoA formation, which was limited to the mitochondrial matrix. This site of activation implies that short chain fatty acids may not depend on carnitine for their oxidation in the mitochondrial matrix, in contrast to long chain fatty acids activated in the outer mitochondrial membrane.