Effect of halofenate and clofibrate on growth and lipid synthesis in Saccharomyces cerevisiae.
Halofenate-free acid (HFA) inhibited the growth of Saccharomyces cerevisiae by 50% at a concentration of 0.34 mm. This inhibitory effect was prevented by addition of either oleate or acetate, but not by pyruvate. When cell growth was supported by oleate, HFA inhibited the incorporation of radioactive carbon from glucose-U-(14)C or pyruvate-2-(14)C into fatty acids and sterols. The incorporation of radioactive carbon into fatty acids and sterols from acetate-2-(14)C was unaffected by the compound. When cell growth was supported by either oleate or acetate, HFA inhibited the conversion of pyruvate-1-(14)C to (14)CO(2). These results suggest that HFA inhibits the conversion of pyruvate to acetate in yeast. Partially purified yeast pyruvate dehydrogenase was inhibited 50% by 5.5 mm HFA; however, the concentration required for 50% inhibition was considerably reduced when the enzyme was preincubated with the compound at room temperature. In a similar manner, the hypolipidemic agent clofibrate-free acid inhibited the growth of yeast by 50% at 3.0 mm. This inhibition was also prevented by acetate and not by pyruvate. In addition, clofibrate-free acid inhibited partially purified pyruvate dehydrogenase by 50% at a concentration of 37.0 mm.
D000085:Acetates / Q000378:metabolism; D002245:Carbon Dioxide / Q000096:biosynthesis; D002247:Carbon Isotopes; D002849:Chromatography, Gas; D002994:Clofibrate / Q000494:pharmacology*; D005227:Fatty Acids / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism; D006016:Glycolates / Q000494:pharmacology*; D006218:Halofenate / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis*; D013058:Mass Spectrometry; D009829:Oleic Acids / Q000378:metabolism; D011771:Pyruvate Oxidase / Q000037:antagonists & inhibitors; D011773:Pyruvates / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis
D000085:Acetates; D002247:Carbon Isotopes; D005227:Fatty Acids; D006016:Glycolates; D000960:Hypolipidemic Agents; D008055:Lipids; D009829:Oleic Acids; D011773:Pyruvates; D013261:Sterols; D002245:Carbon Dioxide; D011771:Pyruvate Oxidase; D002994:Clofibrate; D005947:Glucose; D006218:Halofenate