New Inhibitors of in vitro Conversion of Acetate and Mevalonate to Cholesterol

Abstract

The effects of 1-testololactone, 4-androstene 17[alpha]-o1-3-one-17[beta]-oic acid, and [beta]-hydroxy-[beta]-fluoromethyl-[delta] -valerolactone (fluoromevalonic acid) upon in vitro conversion of labeled acetate and labeled mevalonate into cholesterol were studied using rat liver homogenates. All of these compounds inhibited the acetate conversion, while only the latter 2 inhibited the mevalonate conversion. Fluoromevalonic acid was the most potent inhibitor studied. Fluoroacetate, fluoride ions, and Zn ions had no effect on the mevalonate system while Zn ions inhibited the conversion of acetate to cholesterol.