Effects of the Hypocholesteremic Agent Trifluperidol

Trifluperidol (TFP), at a concentration of 100 ,M, inhibited the 24-h growth of Saccharomyces cerevisiae by about 30%. Effects on lipid metabolism were investigated by monitoring the incorporation of [1-14C]sodium acetate into various lipid fractions after 4 and 24 h ofgrowth in the presence of several concentrations of TFP. Although little effect was noted on the amount of free sterols, 24-h incorporation of label into steryl esters was increased twoto fourfold by 100 ,M TFP. Major sterol components of the steryl ester fraction isolated from an untreated culture were zymosterol (48%) and ergosterol (24%), whereas from the TFP-treated culture A8 24(28)-ergostadienol (66.6%) and A8-ergostenol (14.7%) were most abundant. Free sterols present in the highest concentration in the untreated culture were ergosterol (78.2%) and lanosterol (13%); whereas A8'22_ ergostadienol (38.5%), A8-ergostenol (35.4%), and A8' 24(281-ergostadienol (25.4%) were the most abundant free sterols obtained from the TFP-treated culture. Thus, the major block in the sterol biosynthetic pathway in yeast appears to be A8 -> A7 isomerization. In these same cultures the relative amounts of C12 and C14 acids isolated from both steryl ester and miscellaneous lipid fractions were increased more than threefold over controls.