Monofluoroacetanilidesの毒性発現機構に関する生化学的研究(第3報)

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タイトル別名
  • Studies on the Mechanism of the Monofluoroacetanilides Poisoning to Mammals Part III
  • Monofluoroacetanilides ノ ドクセイ ハツゲン キコウ ニ カンスル セイカガクテキ ケンキュウ 3 Monofluoroacetanilides ノ ビセイブツ サクサン タイシャ エ ノ エイキョウ
  • Effects of Monofluoroacetanilides on the Acetate Metabolism of Microorganisms
  • Monofluoroacetanilidesの微生物酢酸代謝への影響

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説明

In order to ascertain the mechanism of the fluoroacetanilides poisoning, the effects of Na-fluoroacetate (NaFA), fluoroacetanilides, and fluoroacetamide (FAm) on the acetate metabolism of yeast (Saccharomyces cerevisiae) and acetate-grown Arthrobacter ureafaciens were studied by means of the Warburg manometric method. The results were as follows:<br> (1) In case of yeast, the inhibition by NaFA was remarkable. The relationship between inhibition (H) and NaFA concentration in this experiments was approximately shown by the under equation where ∅g was 3×10-5 M and n was 2. (∅g shows the concentration of inhibitor which gives 50% inhibition, and n shows the order of inhibition.)<br> H=1/1+(∅<sub>g/[NaFA])n</sub><br> Although the inhibitions by fluoroacetanilides and FAm were between 1/20 and 1/30 of that by NaFA, the 2 nd order inhibitions were also observed in these compounds. Moreover, the enzymic hydrolysis to fluoroacetanilide in yeast was detected, though it was weak.<br> Therefore, it was estimated that the TCA-cycle in yeast was inhibited not by fluoroacetanilides themselves, but by the liberated fluoroacetate due to the hydrolysis.<br> (2) In case of acetate-grown A. ureafaciens, the acetate consumption was inhibited to the same extent by 10-6 to 10-4M of NaFA, fluoroaceto-P-bromoanilide and FAm. However, the activity of the enzymic hydrolysis was, at least, not recognized more than that in yeast. Different mechanism of the inhibition from that in yeast may exist in this case.<br> (3) It was expected that the biological assay of fluoroacetate may be successful in the range of 1×10-5 to 4×10-4M (0.8 to 30 p. p. m.) by the inhibition test of NaFA on the yeast acetate metabolism.

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