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THE RELATIONSHIP BETWEEN INHIBITION OF PHOSPHOFRUCTOKINASE ACTIVITY AND THE MODE OF ACTION OF TRIVALENT ORGANIC ANTIMONIALS ON SCHISTOSOMA MANSONI
Author(s) -
BUEDING E.,
MANSOUR JOAN M.
Publication year - 1957
Publication title -
british journal of pharmacology and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0366-0826
DOI - 10.1111/j.1476-5381.1957.tb00114.x
Subject(s) - phosphofructokinase , aldolase a , glycolysis , schistosoma mansoni , biochemistry , fructose , chemistry , lactic acid , enzyme , fructose bisphosphate aldolase , biology , bacteria , schistosomiasis , immunology , helminths , genetics
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.