Inhibitory Effects on Lipid Metabolismn in Cultured Cells of ML‐236B, a Potent Inhibitor of 3‐Hydroxt‐3‐methylglutaryl‐Cornzyme‐A Reductase

摘要: Effects of ML-236B, a potent competiove inhibitor 3-hydrocy-3-methyglutaryl-CoA reductase, on the lipiod metabolism were studied using mouse L cells and human smin fibrobalsts. ML-236B completely inhibited sterol sythesis from both [14C]acetate [14C]octanoate in these at tconcentration 0.5 μg/ml (11.117 μM). withour affecting thqat form [14C]mevalonate. Syntheses other lipids adn macromolecules like DNA, RNA protein not affected concentrations up to 5 μg/ml. Concentrations giving 50% inhibitionof synthesis for as low homozygote with familial hypercholesteroloemia. The ML-236B-mediated inhibition syunthesis was readitly reversivle. complkete endogenous higher concentration (5μg/ml) ML-236-B caused marked cell growth even presence exogenous cholesterol contained while gfatel calf serum lipoproteins. This inhivition prevented by teh culture medium mevalonate, but acetate, thus indficating that inhibit specifically interferring mevalonate wynthesis. It is further concluded thjat slight activity synthesis, which provides enfogenous copounds generated meavalonate, may be essential when sufficeient amounts are availavel cells.