Specific inactivation of glucose metabolism from eucaryotic cells by pentalenolactone.
Pentalenolactone, an antibiotic related to the class of the sesquiterpene-lactones and produced by the strain Streptomyces arenae Tü-469, inhibits specifically the glucose metabolism by inactivation of the enzyme glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD oxidoreductase (phosphorylating) ED 1.2.1.1.2). The sensitivity of several eucaryotic cell-systems for pentalenolactone was shown under in vivo conditions. The glycolytic as well as the gluconeogenetic pathway of mammalian cells can be completely inhibited with low concentrations of the antibiotic. In all cases, the minimum inhibitory concentration is dependent on cell density. The inhibitory effect in vivo and in vitro does not seem to be species-specific. In erythrocytes from rats, in Ehrlich-ascites tumor cells and in Plasmodium vinckei infected erythrocytes from mice glycolysis can be inhibited with concentrations of 18--90 micrometers pentalenolactone. In hepatocytes, glycolysis as well as gluconeogenesis in prevented by the same concentrations. In contrast to these results, in yeast the inhibition depends on growth conditions. The inhibition in glucose medium is cancelled by precultivation on acetate-containing medium.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors; D006019:Glycolysis / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008288:Malaria / Q000097:blood; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D012717:Sesquiterpenes
D000900:Anti-Bacterial Agents; D007783:Lactones; D012717:Sesquiterpenes; C017996:arenaemycin E; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005947:Glucose