Synthesis of cholesterol from glucose-U 14C in the liver and extrahepatic tissues of the mouse

The incorporation of glucose-U- 14C into cholesterol and other sterols of liver and extrahepatic tissues has been studied in two experiments in mice fed a purified diet containing 20% corn oil or this diet supplemented with 1% cholesterol or 1% cholestyramine. In each experiment the mice were given 250 mg glucose-U- 14C (20 μCi) orally and killed in 1 hr. Sterols were isolated from various tissues by digitonin precipitation and separated first on silica gel G and then on alumina impregnated with AgNO 3. Cholestanol and Δ 7-cholestenol, which had similar mobilities in these systems, were separated by epoxidation on silica gel G plates. In mice fed the basal diet 2–6 times more cholesterol synthesized from glucose-U- 14C was found in extrahepatic tissues than in the liver. Approximately two-thirds of the extrahepatic labeled cholesterol was found in the gastrointestinal tract. More Δ 7-cholestenol was synthesized from glucose in extrahepatic tissues than the total amount of cholesterol synthesized in liver and carcass combined with approximately two-thirds of the newly synthesized Δ 7-cholestenol found in the skin. Cholesterol feeding reduced the level of radioactivity in liver and carcass cholesterol 90–98% and 35–38% respectively. The overall reduction in cholesterol synthesis in cholesterol-fed mice was 45–55%. Cholestyramine feeding increased the incorporation of label into liver cholesterol 4- to 10-fold and into carcass cholesterol 60–70%. Based on the data obtained in these experiments it has been calculated that in mice fed the control diet, 35–43 μg cholesterol was synthesized out of 250 mg glucose-U- 14C given. Of this newly synthesized cholesterol 5–13 μg were isolated from liver and 30 μg from extra-hepatic tissues.