428
ERNEST BUEDING AND EMMANUEL FÄRBER
ceptors in the regulation of respiration and glycolysis and in the mechanism of the Pasteur and Crabtree eifects in tumor cells. However,
they have not as yet pinpointed the essential basis for the high rates of
glycolysis per se in malignant neoplastic cells.
e. The high rate of glucose uptake by cancer cells (249) has been
suggested as a possible basis for the high rate of glycolysis in tumors
(250). The implication that the high rates of glycolysis in tumor cells
may be due to the high rate of glucose phosphorylation at low concentrations of glucose (251) is compatible with this hypothesis.
The relative importance of glycolysis as compared with respiration
in the generation of energy for the needs of tumor cells has yet to be
defined in a quantitative manner. Because of the high rate of glycolysis
of cancer cells, the proportion of ATP produced by glycolysis is theoretically large in tumors (242). However, the actual energy requirements of cancer cells and the relative amount of this energy generated
by glycolysis is still unknown. Since cancer cells in general appear to
have fewer alternate metabolic pathways for many substrates (252), it
is possible that their energy requirements differ radically from those of
normal cells, qualitatively as well as quantitatively. This factor would
have to be considered in any evaluation of the relative rates of glycolysis
and respiration in energy production.
IV. Species and Tissue Specificities of Glycolytic Enzymes
One of the most fundamental properties of enzymes is their specificity
for a substrate or for a group of substrates. In addition, along with
other proteins, they are endowed with species specificities. Enzymes
which are found in different species are not necessarily identical with
each other, although they catalyze the same reactions, and although they
may have the same substrate specificities. The species specificity of
enzymes is of obvious interest to comparative biochemistry and has
been demonstrated in several studies concerned with properties of homologous glycolytic enzymes.
The first demonstration of the existence of such species differences
among glycolytic enzymes was supplied by Krebs and Najjar (252).
Following immunization of rabbits and chickens with crystalline glyceraldehyde-3-phosphate dehydrogenase of yeast, the serums of these
animals inhibited the activity of this enzyme, but had no effect on
glyceraldehyde-3-phosphate dehydrogenase of rabbit muscle. Similarly,
an antiserum produced against yeast hexokinase had an inhibitory effect
on this enzyme, but did not affect the catalytic activity of brain hexokinase (253). As a result of repeated injections of lactic dehydrogenase
of rabbit muscle into roosters, an antiserum was obtained which markedly
ERNEST BUEDING AND EMMANUEL FÄRBER
ceptors in the regulation of respiration and glycolysis and in the mechanism of the Pasteur and Crabtree eifects in tumor cells. However,
they have not as yet pinpointed the essential basis for the high rates of
glycolysis per se in malignant neoplastic cells.
e. The high rate of glucose uptake by cancer cells (249) has been
suggested as a possible basis for the high rate of glycolysis in tumors
(250). The implication that the high rates of glycolysis in tumor cells
may be due to the high rate of glucose phosphorylation at low concentrations of glucose (251) is compatible with this hypothesis.
The relative importance of glycolysis as compared with respiration
in the generation of energy for the needs of tumor cells has yet to be
defined in a quantitative manner. Because of the high rate of glycolysis
of cancer cells, the proportion of ATP produced by glycolysis is theoretically large in tumors (242). However, the actual energy requirements of cancer cells and the relative amount of this energy generated
by glycolysis is still unknown. Since cancer cells in general appear to
have fewer alternate metabolic pathways for many substrates (252), it
is possible that their energy requirements differ radically from those of
normal cells, qualitatively as well as quantitatively. This factor would
have to be considered in any evaluation of the relative rates of glycolysis
and respiration in energy production.
IV. Species and Tissue Specificities of Glycolytic Enzymes
One of the most fundamental properties of enzymes is their specificity
for a substrate or for a group of substrates. In addition, along with
other proteins, they are endowed with species specificities. Enzymes
which are found in different species are not necessarily identical with
each other, although they catalyze the same reactions, and although they
may have the same substrate specificities. The species specificity of
enzymes is of obvious interest to comparative biochemistry and has
been demonstrated in several studies concerned with properties of homologous glycolytic enzymes.
The first demonstration of the existence of such species differences
among glycolytic enzymes was supplied by Krebs and Najjar (252).
Following immunization of rabbits and chickens with crystalline glyceraldehyde-3-phosphate dehydrogenase of yeast, the serums of these
animals inhibited the activity of this enzyme, but had no effect on
glyceraldehyde-3-phosphate dehydrogenase of rabbit muscle. Similarly,
an antiserum produced against yeast hexokinase had an inhibitory effect
on this enzyme, but did not affect the catalytic activity of brain hexokinase (253). As a result of repeated injections of lactic dehydrogenase
of rabbit muscle into roosters, an antiserum was obtained which markedly