Abstract
A β-lactone isolated from Scopulariopsis sp. shows a potent inhibition of cholesterogenesis. The structure of this β-lactone, termed F-244, is 3,5,7-trimethyl-12-hydroxy-13-hydroxymethyl-2,4-tetradecadiendioic acid 12,14-lactone. The inhibition site of F-244 in cholesterol synthesis was studied. The growth of Vero cells was inhibited at 6.25-12.5 μg/ml of F-244. The inhibition of growth was overcome by the addition of mevalonate to the culture medium, but not by the addition of acetate. In a rat liver enzyme system, the incorporations of [14C]acetate and [14C]acetyl-CoA into digitonin-precipitable sterol were 50% inhibited by 0.58 βg/ml of F-244. The incorporation of [14C]mevalonate was not affected. Studies on the effects of F-244 on the three enzymes involved in mevalonate biosynthesis demonstrated that the drug specifically inhibits HMG-CoA synthase with IC50 value of 0.065 μg /ml. The effect of analogs of F-244 on HMG-CoA synthase was also investigated.
Original language | English (US) |
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Pages (from-to) | 351-356 |
Number of pages | 6 |
Journal | Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism |
Volume | 922 |
Issue number | 3 |
DOIs | |
State | Published - Dec 14 1987 |
Keywords
- Cholesterol biosynthesis
- F-244
- HMG-CoA synthase
- Hydroxymethylglutaryl-CoA reductase
- Hydroxymethylglutaryl-CoA synthase
- Inhibitor
- β-Lactone
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Endocrinology