ACYL COA AND LIPID-SYNTHESIS FROM KETONE-BODIES BY THE EXTRAMITOCHONDRIAL FRACTION OF HEPATOMA TISSUE

The compartmentation of the pathway for the synthesis of lipids from k etone bodies was examined in a cell free, post-mitochondrial supernata nt fraction of malignant Morris hepatoma 7777 tissue. A fortified supe rnatant system effectively incorporated radioactive D(-)-3-hydroxybuty rate and acetoacetate into cholesterol and fatty acids, and both keton e bodies were directly converted to their CoA thioesters. Furthermore, a microsome-free (100,000 Xg) cytosolic fraction was also able to acy late 3-hydroxybutyrate to 3-hydroxybutyryl CoA. No previous identifica tion of this enzyme activity has been described. These results which c haracterize a distinct extramitochondrial pathway for conversion of 3- hydroxybutyrate as well as acetoacetate into lipids also suggest the p ossibility of a previously undetected enzymatic activity for utilizati on of this ketone body. (C) 1996 Academic Press, Inc.