The effect of some cofactors on the synthesis of fatty acids and cholesterol in cell‐free preparations of rat liver

Brady (1958) and Wakil (1958) have shown that cell-free preparations of pigeon liver synthesize long-chain fatty acids through a pathway which includes the formation of malonyl co-enzyme A (CoA) from acetyl CoA and CO2. It has also been shown that biotin and Mn2+ are required for this carboxylation (Wakil, Titchener & Gibson, 1958; Brady, 1958; Wakil, 1958). We have recently shown that the synthesis of cholesterol and fatty acids by cell-free fractions ofrat liver can be modified by injecting the rats with thyroxine before the livers are removed (Fletcher & Myant, 1960). When the rats are given 20 ,g of thyroxine, there is an increase in cholesterol synthesis and a fall in fatty acid synthesis. With doses of 30 ,g or more both syntheses are usually depressed. In order to interpret these results it was necessary to know whether our cell-free fractions of rat liver synthesize fatty acids by the same pathway as that followed in the preparations of pigeon liver used by Brady (1958) and by Wakil (1958). The effect of small doses of thyroxine also raised the question as to how far the two biosynthetic pathways are linked by competition for common cofactors or precursors. If they are so linked, it might be expected that when the rate of one biosynthesis is modified, that of the other would tend to change in the opposite direction. In this paper we describe the effect of various cofactors on the synthesis of fatty acids and cholesterol in cell-free fractions of rat liver.