FATTY ACID SYNTHESIS FROM ACETATE BY HUMAN LIVER HOMOGENATE FRACTIONS*

Abstract

Homogenates of human liver were separated into mitochondrial, microsomal, and particle-free supernatant fractions. These fractions were incubated in a medium fortified with cofactors and oxidizable substrates, and their capacities to synthesize fatty acids from acetate were studied. A stimulatory effect of microsomes upon the conversion of acetate carbon to fatty acids by the particle-free, supernatant fraction isolated from human liver was demonstrated. Addition of micro-somes beyond a certain level resulted, however, in inhibition of the fatty acid synthesis. The addition of either citrate, isocitrate, or aconitate, in addition to TPNH, was an obligatory requirement in order to obtain high levels of fatty acid synthesis in the human composite system (supernatant fraction plus microsomes). Glucose-6-phosphate failed to serve as a substitute for this citrate requirement, as also did a combination of glucose-6-phosphate, glucose-6-phosphate dehydrogenase, CO2, and [alpha]-ketoglutarate. As shown previously in rat liver, TPNH generation does not limit fatty acid synthesis from acetate by the human liver composite system. The participation of CO2 in the conversion of acetate carbon to fatty acids by human liver is suggested by the demonstration of an avidin inhibition which was reversed by the addition of biotin.