Inhibition of sterol biosynthesis by bacitracin.
Bacitracin is an inhibitor of the biosynthesis of squalene and sterols from mevalonic acid, C(5)-isopentenyl pyrophosphate, or C(15)-farnesyl pyrophosphate catalyzed by preparations from rat liver. The antibiotic is active at extremely low ratios of antibiotic to substrate. The mechanism of inhibition appears to be the formation of a complex between bacitracin, divalent cation, and C(15)-farnesyl pyrophosphate and other isoprenyl pyrophosphates. It is similar to the formation of the complex with C(55)-isopropenyl pyrophosphate in microbial systems. The toxicity of bacitracin for animal cells could be due in part to the formation of these complexes.
D000469:Alkaline Phosphatase / Q000494:pharmacology; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology*; D002247:Carbon Isotopes; D003864:Depression, Chemical; D011756:Diphosphates / Q000096:biosynthesis; D004926:Escherichia coli / Q000201:enzymology; D005204:Farnesol / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013185:Squalene / Q000096:biosynthesis; D013261:Sterols / Q000096:biosynthesis*; D013729:Terpenes / Q000096:biosynthesis; D014316:Tritium
D002247:Carbon Isotopes; D011756:Diphosphates; D009596:Nitrophenols; D013261:Sterols; D013729:Terpenes; D014316:Tritium; D001414:Bacitracin; D005204:Farnesol; D013185:Squalene; D000469:Alkaline Phosphatase; D010744:Phosphoric Monoester Hydrolases; D008798:Mevalonic Acid