Inhibition of sterol synthesis by citrinin in a cell-free system from rat liver and yeast.
Citrinin, a fungal 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, two 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 although higher concentrations of the antibiotic were required for inhibition.
D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism*; D000123:Acetyltransferases / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis*; D002953:Citrinin / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*
D001578:Benzopyrans; D002953:Citrinin; D002784:Cholesterol; D000429:Alcohol Oxidoreductases; D006903:Hydroxymethylglutaryl CoA Reductases; D000123:Acetyltransferases; D000101:Acetyl-CoA C-Acetyltransferase