Ethambutolの作用様式 (続報)

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Gale & McLain (J. Bact., 86: 749, 1963) observed that nuclear zone of M. smegmatis disappeared electron-microscopically under the presence of ethambutol, and Forbes et al. (J. Bact., 89: 1299, 1965) reported that the incorporations of phosphate-32P into nucleic acids and of sulfate-35S into proteins of M. smegmatis were suppressed by ethambutol. These findings suggested that ethambutol may affect nucleic acid synthesis. Recently, Tsukamura & Mizuno (Kekkaku, 42: 437, 1967) observed that the incorporations of glycine-1-14C into nucleic acids and of several radioactive amino acids into proteins of M. smegmatis were inhibited by ethambutol. It was also suggested that the formation of glutamic acid from acetate-1-14C was not inhibited but the incorporation of radioactive glutamic acid into proteins was inhibited by ethambutol. Furthermore, it was shown that the incorporation of methionine-35S into lipids was inhibited by ethambutol. This last finding suggested that ethambutol may affect not only nucleic acid gynthesis but also lipid synthesis. The present study has been designed to observe changes appearing primarily under the presence of ethambutol. The strain used was Mycobacterium smegmatis strain Jucho. The methods used were described previously (Tsukamura & Mizuno: Kekkaku, 42: 437, 1967). Fractionation was made according to Schneider (J. Biol. Chem., 161: 293, 1945). The results obtained are shown in figures 1 to 4, and are summarized in Table. It was confirmed that the lipid metabolism in M. smegmatis is disturbed by ethambutol. The effect was observed as early as 3 hours after contact with the drug, and the incorporation of acetate-1-14C into lipid fraction was increased significantly. After this change, decrease of incorporation of glycine-1-14C and acetate-1-14C into nucleic acid fraction and decrease in incorporation of glycine-1-14C, acetate-1-14C, leucine-1-14C and methionine-35S into protein fraction were observed. The effect of ethambutol on lipid metabolism was observed also as decrease in incorporation of methionine-35S into lipids. In conclusion: Ethambutol inhibited lipid, nucleic acid and protein metabolisms in M. smegmatis. Among these effects, disturbance in lipid metabolism appeared at first, which was observed as an increase in incorporation of acetate-1-14C into lipids. Inhibition of incorporation of methionine-35S into lipids also was confirmed. It is noteworthy that ethambutol inhibits lipid metabolism in M. smegmatis.
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Ethambutolの作用様式 (続報)

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