AFFINITY OF 3-BETA-(2-HYDROXYETHOXY)-5-AL PHA-CHOLEST-8(14)-EN-15-ONETO OXYSTEROL BINDING-PROTEIN AND ITS METABOLISM IN HEPATOMA HEP G2 CELLS

beta-(2-Hydroxyethoxy)-5 alpha-cholest-8(14)-en-15-one, a synthetic in hibitor of cholesterol biosynthesis, was shown to exhibit a high affin ity to oxysterol binding protein. This was proved by ultracentrifugati on of the protein fraction from rabbit liver in the presence of the H- 3-labeled inhibitor, 3 beta-(2-hydroxy-2-[H-3]ethoxy)-5 alpha cholest- 8(14)-en -15-one, or by the substitution of the [H-3]-25-hydroxycholes terol in its complex with the oxysterol binding protein. In human hepa toma Hep G2 cells, the inhibitor decreased activity of 3-hydroxy-3-met hylglutaryl CoA reductase [ID50 (2.7 +/- 0.7) x 10(-5) M] and was tran sformed into 3 beta-[2-(9-Z-octadecenoyloxy)ethoxy]-5 alpha-cholest-8( 14)-en-15-one.