Synthesis of lanosterol in vivo.

Lanosterol and related CzO sterols occur in considerable quantity in wool fat but have not so far been isolated from the principal sites of sterol biogenesis in the animal body. Evidence for the presence of this type of sterol in internal organs does, however, exist, since the formation of lanosterol from acetate and its conversion to cholesterol in homogenates of rat liver have recently been demonstrated (l-3). If, as appears likely, the concentration of lanosterol in the tissues is small, and if, in the biosynthesis of cholesterol, lanosterol is an obligatory intermediate, its rate of turnover should be relatively fast. This expectation has been borne out by the present experiments. Acetate-Cl4 was injected into rats and the animals were killed 10 minutes later. Under these conditions, lanosterol and also squalene contribute significantly to the radioactivity of the unsaponifiable fraction of intestinal tissue and of liver. On the other hand, at longer time intervals after a single injection of acetate, the radioactivities of lanosterol and of squalene account for less than 2 per cent of the Cl4 content of this fraction. The present experiments have also revealed at least one new constituent in the unsaponifiable matter which is an intermediate in the demethylation of lanosterol to cholesterol.