Inhibition of cholesterol synthesis in cultured cells by 25-azidonorcholesterol.
25-Azidonorcholesterol, a side chain analogue of cholesterol, inhibits cholesterol biosynthesis in BHK 21 cells in tissue culture; but 3-azido-5-cholestene, the azido analogue of cholesterol has no inhibitory effect. Cell growth was unimpaired by the azido analogue, which showed only a minimal uptake by the cell, compared with that of cholesterol or 25-azidonorcholesterol. 25-Azidonorcholesterol is incorporated into the membranes of BHK 21 cells in place of cholesterol as demonstrated by isotope experiments. The incorporation of radioactive acetate is strongly inhibited by the side chain azido substituted cholesterol derivative; the incorporation of radioactive mevalonate is, however, unimpaired. We conclude that the inhibition occurs at the hydroxymethylglutaryl-CoA-reductase step. Cell growth is not significantly altered.
D000818:Animals; D000924:Anticholesteremic Agents; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives / Q000096:biosynthesis; D003065:Coenzyme A; D008099:Liver / Q000378:metabolism; D051381:Rats
D000924:Anticholesteremic Agents; D002784:Cholesterol; D003065:Coenzyme A