Buthiobate: a potent inhibitor for yeast cytochrome P-450 catalyzing 14 alpha-demethylation of lanosterol.
Buthiobate (S-n-butyl S'-p-tert-butylbenzyl N-3-pyridyldithiocarbon-imidate), a fungicide, inhibited 14 alpha-demethylation of lanosterol catalyzed by a reconstituted enzyme system consisting of cytochrome P-450 (P-450(14)-DM) and NADPH-cytochrome P-450 reductase both purified from Saccharomyces cerevisiae. Concentration of buthiobate necessary for the 50% inhibition was 0.3 microM and this value was markedly lower than those of metyrapone and SKF-525A. Buthiobate bound stoichiometrically to P-450(14)-DM and induced Type II spectral change of the cytochrome. Buthiobate inhibited lanosterol-dependent enzymatic reduction of the cytochrome. These facts indicate that buthiobate binds to P-450(14)-DM with high affinity and acts as a potent inhibitor on the cytochrome.
D065607:Cytochrome P-450 Enzyme Inhibitors; D005659:Fungicides, Industrial / Q000494:pharmacology*; D007096:Imidoesters / Q000494:pharmacology*; D007810:Lanosterol / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D058886:Sterol 14-Demethylase
D065607:Cytochrome P-450 Enzyme Inhibitors; D005659:Fungicides, Industrial; D007096:Imidoesters; C016349:buthiobate; D007810:Lanosterol; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase