Inhibition of Sterol Synthesis in Cultured Mouse Cells by Cholesterol Derivatives Oxygenated in the Side Chain

Sterols derived from cholesterol by hydroxylation of the side chain in the 20 α, 22α, 22β, or 25 position inhibited sterol synthesis from acetate and depressed the level of 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.34) activity in primary cultures of mouse fetal liver cells and in L cell cultures.

Abstract

Abstract Sterols derived from cholesterol by hydroxylation of the side chain in the 20α, 22α, 22β, or 25 position inhibited sterol synthesis from acetate and depressed the level of 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) activity in primary cultures of mouse fetal liver cells and in L cell cultures. Rates of acetate metabolism to fatty acids and CO2, and rates of RNA and protein synthesis were not affected. Following the addition of the most potent inhibitors of the group, 25-hydroxycholesterol and 20α-hydroxycholesterol, to l cell cultures the enzyme activity diminished to one-half of the original amount within a period of 1 to 1.3 hours. Inhibitory potency was influenced by the location of the hydroxyl function on the side chain, by the completeness of the side chain, and by the introduction of a third functional group into the molecule.