Inhibition of Sterol Biosynthesis by Bacitracin

Bacitracin is an inhibitor of the biosynthesis of squalene and sterols from mevalonic acid, C₅-isopentenyl pyrophosphate, or C₁₅-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 C₁₅-farnesyl pyrophosphate and other isoprenyl pyrophosphates. It is similar to the formation of the complex with C₅₅-isopropenyl pyrophosphate in microbial systems. The toxicity of bacitracin for animal cells could be due in part to the formation of these complexes.