1. 1. Liver slices from fasted rats which had been injured 24 h before killing by hind limb ischaemia or laparotomy showed a 10-fold increase in the incorporation of [2-14C] acetate into cholesterol, with no change in the conversion of the label to 14C02 and long-chain fatty acids. 2. 2. The conversion of dl-[2-14C]mevalonate to cholesterol by liver slices was also increased after injury but less markedly than observed with acetate. 3. 3. The stimulation of the incorporation of acetate into cholesterol caused by injury was inhibited by the administration of ethionine, by large doses of actinomycin D and by dietary cholesterol but was not dependent on the presence of thyroid, hypophysis or adrenals. 4. 4. An increased incorporation of acetate into both liver and serum cholesterol was also observed in vivo after injury. After a single injection of labelled acetate, the changes in liver and serum cholesterol specific activity were followed in time in both control and injured animals; a different pattern was observed in the two groups, and the results were compatible with a greater turnover rate of cholesterol in the injured animals. 5. 5. Direct evidence for an increased rate of cholesterol breakdown after injury was obtained by injecting [26-14C]cholesterol and by measuring the amount of label expired as 14CO2. Injured animals converted [26-14C]cholesterol to 14CO2 at a greater rate than did their controls. 6. 6. It is concluded that the rate of both synthesis and breakdown of cholesterol are increased after physical injury. The possibility is considered that increased cholesterol breakdown may be responsible for the accelerated cholesterol formation by decreasing the concentration of cholesterol at the site, within the liver, where it exercises a feedback control on its own synthesis. © 1969.
