Acyl CoA and Lipid Synthesis from Ketone Bodies by the Extramitochondrial Fraction of Hepatoma Tissue

Abstract

The compartmentation of the pathway for the synthesis of lipids from ketone bodies was examined in a cell free, post-mitochondrial supernatant fraction of malignant Morris hepatoma 7777 tissue. A fortified supernatant system effectively incorporated radioactive D(−)-3-hydroxybutyrate and acetoacetate into cholesterol and fatty acids, and both ketone bodies were directly converted to their CoA thioesters. Furthermore, a microsome-free (100,000 ×g) cytosolic fraction was also able to acylate 3-hydroxybutyrate to 3-hydroxybutyryl CoA. No previous identification of this enzyme activity has been described. These results which characterize a distinct extramitochondrial pathway for conversion of 3-hydroxybutyrate as well as acetoacetate into lipids also suggest the possibility of a previously undetected enzymatic activity for utilization of this ketone body.