The effect of clotrimazole and triadimefon on 3-hydroxy-3-methyl-glutaryl-CoA-reductase-[EC 1.1.1.34]-activity in Saccharomyces cerevisiae.
Clotrimazole and triadimefon are known as potent inhibitors of ergosterol synthesis in pathogenic yeast and fungi, respectively. As their mode of action generally the inhibition of sterol desmethylation reactions is accepted. We report about a second effect, a "feed-back" inhibition of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA-reductase by accumulation of ergosterol precursors. Addition of lanosterol to intact cells leads to an inhibition of HMG-CoA-reductase as well, but not to fungistatic effects. From the reported data the influences of clotrimazole and triadimefon have to be considered as an inhibition of desmethylation reactions involved in ergosterol synthesis of yeast and fungi with a concomitant decreased production of mevalonate.
D002458:Cell Fractionation; D003022:Clotrimazole / Q000494:pharmacology*; D004875:Ergosterol / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D007810:Lanosterol / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D014230:Triazoles / Q000494:pharmacology*
D007093:Imidazoles; D014230:Triazoles; C032910:triadimefon; D007810:Lanosterol; D006903:Hydroxymethylglutaryl CoA Reductases; D003022:Clotrimazole; D004875:Ergosterol