430
ERNEST BUEDING AND EMMANUEL FÄRBER
these enzymes are identical. This applies to the phosphoglucose isomerases of Schistosoma mansoni and of rabbit muscle (180). The dissociation constants of the substrates are identical, as are the equilibrium
constants of both enzymes, and there are close similarities in the pH
optima. Thus, the two enzymes can be distinguished from each other
only by specific antibodies. On the other hand, when differences in
kinetics or in cofactor requirements of homologous enzymes are observed, the question may be raised whether or not their active centers
are identical. Kinetic differences have been reported in the cases of
lactic dehydrogenases (257) and of the phosphofructokinases (181) of
schistosomes and rabbit muscle.
The aldolases of mammalian muscle (258, 259), of Trypanosoma
cruzi (260), and of plants (261, 262) have no metal requirements,
while the activities of the aldolases of yeast (258), of Clostridium perfringens (263), of Aspergillus niger (264), and of trichomonads (265,
266) are inhibited by metal-binding compounds, such as α,α-dipyridyl.
This inhibition is reversed by Fe
2+ . While the latter is the only divalent
metal activating the clostridial aldolase (263), the enzymes catalyzing
the same reaction in yeast and in Aspergillus are activated also by Zn
2+ ,
Co
2+ , and Mn
2+ (258, 264). An even greater degree of difference in the
nature of the active center must prevail when variations in the substrate
specificity are encountered among homologous enzymes. Such is the case
with the hexokinases of various species and tissues. Some of these enzymes [yeast (267, 268), brain (267)] catalyze the phosphorylation of
glucose, fructose, mannose, glucosamine, and desoxyglucose. On the
other hand, numerous hexokinases from other tissues and organisms have
a high specificity for a single hexose (179, 269-281).
Differences in the nature of homologous enzymes of various species
should be reflected in variations in susceptibility of these enzymes to
certain inhibitors. This is illustrated not only by the effect of metalbinding agents on aldolases (see above), but also by the actions of organic antimonials on phosphofructokinases (282). Low concentrations
of these compounds markedly inhibit the activity of the schistosome
phosphofructokinase, while interference with the catalytic activity of
the host's phosphofructokinase occurs only with much higher concentrations or does not occur at all. This differential susceptibility of the
phosphofructokinase of the parasite to antimonials can account for the
chemotherapeutic action of the latter in schistosomiasis. Glycolysis supplies the major source of energy for the organism and the rate of the
phosphofructokinase reaction determines the rate of glycolysis of the
parasite. Inhibition of phosphofructokinase activity of schistosomes by
antimonials is demonstrable also in the intact parasite because admin-
ERNEST BUEDING AND EMMANUEL FÄRBER
these enzymes are identical. This applies to the phosphoglucose isomerases of Schistosoma mansoni and of rabbit muscle (180). The dissociation constants of the substrates are identical, as are the equilibrium
constants of both enzymes, and there are close similarities in the pH
optima. Thus, the two enzymes can be distinguished from each other
only by specific antibodies. On the other hand, when differences in
kinetics or in cofactor requirements of homologous enzymes are observed, the question may be raised whether or not their active centers
are identical. Kinetic differences have been reported in the cases of
lactic dehydrogenases (257) and of the phosphofructokinases (181) of
schistosomes and rabbit muscle.
The aldolases of mammalian muscle (258, 259), of Trypanosoma
cruzi (260), and of plants (261, 262) have no metal requirements,
while the activities of the aldolases of yeast (258), of Clostridium perfringens (263), of Aspergillus niger (264), and of trichomonads (265,
266) are inhibited by metal-binding compounds, such as α,α-dipyridyl.
This inhibition is reversed by Fe
2+ . While the latter is the only divalent
metal activating the clostridial aldolase (263), the enzymes catalyzing
the same reaction in yeast and in Aspergillus are activated also by Zn
2+ ,
Co
2+ , and Mn
2+ (258, 264). An even greater degree of difference in the
nature of the active center must prevail when variations in the substrate
specificity are encountered among homologous enzymes. Such is the case
with the hexokinases of various species and tissues. Some of these enzymes [yeast (267, 268), brain (267)] catalyze the phosphorylation of
glucose, fructose, mannose, glucosamine, and desoxyglucose. On the
other hand, numerous hexokinases from other tissues and organisms have
a high specificity for a single hexose (179, 269-281).
Differences in the nature of homologous enzymes of various species
should be reflected in variations in susceptibility of these enzymes to
certain inhibitors. This is illustrated not only by the effect of metalbinding agents on aldolases (see above), but also by the actions of organic antimonials on phosphofructokinases (282). Low concentrations
of these compounds markedly inhibit the activity of the schistosome
phosphofructokinase, while interference with the catalytic activity of
the host's phosphofructokinase occurs only with much higher concentrations or does not occur at all. This differential susceptibility of the
phosphofructokinase of the parasite to antimonials can account for the
chemotherapeutic action of the latter in schistosomiasis. Glycolysis supplies the major source of energy for the organism and the rate of the
phosphofructokinase reaction determines the rate of glycolysis of the
parasite. Inhibition of phosphofructokinase activity of schistosomes by
antimonials is demonstrable also in the intact parasite because admin-