Mechanism of action of CM-55, a synthetic analogue of the antilipogenic antibiotic cerulenin.
CM-55 is a synthetic analogue of the antibiotic cerulenin with the chemical structure of 2, 3-dodecenyl-4-oxo-dimethyl amide. This compound inhibited the growth of Saccharomyces cerevisiae ATCC 12341 and inhibited protein and lipid synthesis by 91 and 95%, respectively, at a concentration of 50 mug/ml (2.1 x 10(-4) M). The inhibition of protein synthesis was associated with the partial reduction of ribonucleic acid synthesis and leucine transport. The mechanism of inhibition of lipid synthesis was further investigated in a cell-free extract of the yeast. CM-55 inhibited the incorporation of [(14)C]acetyl Coenzyme A (CoA) into both fatty acid (FAF) and non-saponifiable fractions (NSF). However, it did not inhibit [(14)C]malonyl CoA incorporation into FAF and only slightly inhibited [(14)C]mevalonate incorporation into NSF. The activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase was inhibited more strongly than the incorporation of [(14)C]3-hydroxy-3-methylglutaryl CoA into NSF; this could account for the CM-55 inhibition of [(14)C]acetyl CoA incorporation into NSF.
D000085:Acetates / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000037:antagonists & inhibitors; D002569:Cerulenin / Q000494:pharmacology*; D005227:Fatty Acids / Q000096:biosynthesis; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000037:antagonists & inhibitors; D007930:Leucine / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis
D000085:Acetates; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D013261:Sterols; D002569:Cerulenin; D000101:Acetyl-CoA C-Acetyltransferase; D006904:Hydroxymethylglutaryl-CoA Synthase; D007930:Leucine