BUEDING E, MANSOUR J M
Br J Pharmacol Chemother. 1957 Jun;12(2):159-65. doi: 10.1111/j.1476-5381.1957.tb00114.x.
The addition of purified mammalian phosphofructokinase to homogenates of schistosoma mansoni increased the rate of lactic acid production from glucose and reversed the inhibition of glycolysis produced by low concentrations of trivalent organic antimonials. Neither mammalian phosphofructokinase nor trivalent antimonials affected the rate of lactic acid production from fructose-1:6-diphosphate (HDP) by schistosome homogenates. Accordingly, in the schistosome, the rate of glycolysis of glucose is determined by the activity of phosphofructokinase.The aldolase of S. mansoni has a high requirement for HDP; relatively slight reductions in the concentration of this substrate below the optimum resulted in a sharp decline of aldolase activity. Therefore, decreased formation of HDP, due to inhibition of schistosome phosphofructokinase activity by antimonials, reduced the activity of aldolase and resulted in an inhibition of glycolysis of schistosome homogenates.Kinetic data revealed differences in the nature of the phosphofructokinase of S. mansoni and that of the enzyme catalysing the same reaction in the host. Exposure of schistosomes to low concentrations of potassium antimonyl tartrate or administration of subcurative doses of stibophen to the host resulted in an accumulation of the substrate (fructose-6-phosphate), and a reduction of the product (HDP) of the phosphofructokinase reaction, indicating that the activity of this enzyme was inhibited by antimonials in the intact parasite. It is concluded that inhibition of phosphofructokinase activity can account for the mechanism of the chemotherapeutic action of trivalent organic antimonials in schistosomiasis.
向曼氏血吸虫匀浆中添加纯化的哺乳动物磷酸果糖激酶，可提高葡萄糖产生乳酸的速率，并逆转低浓度三价有机锑化合物对糖酵解的抑制作用。哺乳动物磷酸果糖激酶和三价锑化合物均不影响血吸虫匀浆由1,6 - 二磷酸果糖（HDP）产生乳酸的速率。因此，在血吸虫中，葡萄糖的糖酵解速率由磷酸果糖激酶的活性决定。曼氏血吸虫的醛缩酶对HDP有很高的需求；该底物浓度相对轻微地降至最适浓度以下，会导致醛缩酶活性急剧下降。因此，由于锑化合物抑制血吸虫磷酸果糖激酶活性而导致HDP生成减少，从而降低了醛缩酶的活性，并导致血吸虫匀浆的糖酵解受到抑制。动力学数据显示，曼氏血吸虫的磷酸果糖激酶与宿主中催化相同反应的酶在性质上存在差异。将血吸虫暴露于低浓度的酒石酸锑钾或给宿主施用亚治疗剂量的锑波芬，会导致底物（6 - 磷酸果糖）积累，以及磷酸果糖激酶反应产物（HDP）减少，这表明该酶的活性在完整寄生虫中受到锑化合物的抑制。得出的结论是，磷酸果糖激酶活性的抑制可以解释三价有机锑化合物在血吸虫病化疗作用中的机制。
