INHIBITION OF STEROL SYNTHESIS BY CITRININ IN A CELL-FREE SYSTEM FROM RAT-LIVER AND YEAST

Abstract

Citrinin, a fungal [Pythium ultimum] metabolite known as an antibiotic, strongly inhibited the labeled acetate incorporation into nonsaponifiable lipids by a cell-free system from rat liver but not the labeled mevalonate incorporation. Of the enzymes involved in cholesterol synthesis, 2 enzymes, acetoacetyl-CoA thiolase (EC 2.3.1.9) and 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34), were specifically inhibited by the antibiotic. The concentration required for 50% inhibition was 0.2 mM for the former enzyme and 0.5 mM for the latter. Essentially the same results were obtained with a cell-free system from yeast [Saccharomyces cerevisiae], although higher concentrations of the antibiotic were required for inhibition.