[Inhibitory effect of bithionol on NADH-fumarate reductase in ascarides].
[Inhibitory effect of bithionol on NADH-fumarate reductase in ascarides].
复制标题
联硫醇对蛔虫NADH-富马酸还原酶的抑制作用[J].
DOI：
10.1248/yakushi1947.113.9_663
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Y. Murakoshi
中科院分区：
文献类型：
--
作者：
K. Ikuma;M. Makimura;Y. Murakoshi
为阐明二硫醇的驱虫作用机制，测定了二硫醇对猪蛔虫NADH-富马酸还原酶(NADH-FR)的抑制作用。NADH-FR是一种无氧碳水化合物代谢途径的酶，用脱氧胆酸从虫体线粒体中溶解，然后用单乙醇胺-Sepharose4B柱层析进行部分纯化。从酶蛋白和磷脂中分离出从NADH到富马酸的电子转移所需的罗丹酚(Rhodoquone，RQ)。虽然从上述柱子洗脱的酶蛋白部分没有显示NADH-FR活性，但该酶可通过加入纯化的RQ和磷脂酰胆碱而重新激活。二硫醇对重组NADH-FR的IC50值为18+/-2微米。抑制类型与RQ呈竞争性。即使在150微米的高浓度下，二硫醇对不需要RQ的30%NADH-铁氰化钠还原酶的抑制率也高达30%。这些结果表明，酚类驱虫剂二硫代酚的药理作用依赖于与RQ竞争抑制电子传递系统。
To elucidate the mechanism of anthelmintic action of bithionol, the inhibitory effect of the drug on NADH-fumarate reductase (NADH-FR) of Ascaris lumbricoides suum was examined. NADH-FR, an enzyme of anaerobic carbohydrate metabolic pathway was solubilized from the mitochondria of the worm's muscle with deoxycholate, and then partially purified with the monoethanolamine-Sepharose 4B column chromatography. Rhodoquinone (RQ), which is required for the electron transfer from NADH to fumarate, was separated from the enzyme protein and phospholipids. Although the enzyme protein fraction eluted from the above column did not show NADH-FR activity, this enzyme was reactivated by the addition of purified RQ and phosphatidylcholine. The IC50 value of bithionol for reconstituted NADH-FR was 18 +/- 2 microM. The inhibition type was competitive to RQ. Bithionol inhibited at most 30% NADH-ferricyanide reductase, which did not require RQ, even at high concentration of 150 microM. These results suggest that the pharmacological action of bithionol, a phenolic anthelmintic, depends on the inhibition of the electron transport system by the competition with RQ.