The role of squalene synthetase in the inhibition of tetrahymanol biosynthesis by cholesterol in Tetrahymena pyriformis.

The biosynthesis of the triterpenoid alcohol tetrahymanol by Tetrahymena pyriformis is rapidly inhibited by the addition of cholesterol to the growth medium. The primary site of this inhibition by cholesterol has been established to be at the level of the enzyme squalene synthetase. The protein synthesis inhibitor cycloheximide produces an identical decline in squalene synthetase activity to that of cholesterol and the half-life of the enzyme is about 50 minutes. No direct inhibition of the enzyme is observed and suggests that cholesterol inhibits the actual synthesis of the enzyme squalene synthetase. Farnesol is accumulated during in vitro incubations derived from cells grown in the presence of cholesterol or cycloheximide.