9. COMPARATIVE BIOCHEMISTRY OF GLYCOLYSIS
427
the surviving cells. So far this effect has been reported only rarely {223,
224, 229) in normal tissues.
The basis for the increased rate of glycolysis in tumors is still not
established. The following are some of the possible factors that have
been considered: (a) a. different mechanism of glycolysis in tumors
than in normal tissues; (b) different properties, such as rates or substrate-enzyme affinities, in the enzymes of the two kinds of tissues; (c)
increased amounts of the rate-limiting enzymes and other enzymes of
glycolysis; (d) alterations in the intracellular regulation of the metabolic
pathways; or (e) alterations in the permeability of cancer cells.
a. Qualitatively, it is generally accepted that the enzymatic mechanisms of glycolysis in tumors are the same as those in normal tissues
(230-234), despite the occasional claims for "nonphosphorylating glycolysis" and other alternate schemes for the Embden-Meyerhof pathway (235, 236).
b. In the very few instances where homologous enzymes of tumors
and of normal tissues have been studied, the enzymes from malignant
tissues were found to be indistinguishable immunologically from those of
normal tissues of the same species (237, 238).
c. Studies of the activities of glycolysis or of one or more of the glycolytic enzymes in cell-free preparations have yielded confusing results.
For example, LePage has found that homogenates of many normal rat
tissues produced as much as or more lactic acid than did homogenates
of several malignant rat tumors when incubated anaerobically in the
presence of hexosediphosphate, glucose, pyruvate, and fluoride (234).
Also, lactic dehydrogenase activity of several malignant tissues was in
the same range as that of normal tissues (206). In contrast, some studies
have demonstrated considerably higher activities for many of the glycolytic enzymes of malignant tissues as compared to homologous normal
tissues (239-241). Also, a high-malignancy tumor line grown in tissue
culture was reported to have considerably more activity with regard to
some glycolytic enzymes than did a more normal line of cells (242).
The resolution of this apparent discrepancy between the results of several investigators will be of considerable importance for the eventual
interpretation of the significance of the high rate of glycolysis in cancer
tissue.
d. Several recent studies have been concerned with clarifying the possible role of intracellular factors, such as the level of inorganic phosphate and the levels of ATP and ADP, upon the balance between respiration and glycolysis in the intact cells [(27, 28, 243-248); see also
Section II above]. These investigators indicate a probable critical role of
the concentrations of inorganic phosphate and/or of phosphate ac-
427
the surviving cells. So far this effect has been reported only rarely {223,
224, 229) in normal tissues.
The basis for the increased rate of glycolysis in tumors is still not
established. The following are some of the possible factors that have
been considered: (a) a. different mechanism of glycolysis in tumors
than in normal tissues; (b) different properties, such as rates or substrate-enzyme affinities, in the enzymes of the two kinds of tissues; (c)
increased amounts of the rate-limiting enzymes and other enzymes of
glycolysis; (d) alterations in the intracellular regulation of the metabolic
pathways; or (e) alterations in the permeability of cancer cells.
a. Qualitatively, it is generally accepted that the enzymatic mechanisms of glycolysis in tumors are the same as those in normal tissues
(230-234), despite the occasional claims for "nonphosphorylating glycolysis" and other alternate schemes for the Embden-Meyerhof pathway (235, 236).
b. In the very few instances where homologous enzymes of tumors
and of normal tissues have been studied, the enzymes from malignant
tissues were found to be indistinguishable immunologically from those of
normal tissues of the same species (237, 238).
c. Studies of the activities of glycolysis or of one or more of the glycolytic enzymes in cell-free preparations have yielded confusing results.
For example, LePage has found that homogenates of many normal rat
tissues produced as much as or more lactic acid than did homogenates
of several malignant rat tumors when incubated anaerobically in the
presence of hexosediphosphate, glucose, pyruvate, and fluoride (234).
Also, lactic dehydrogenase activity of several malignant tissues was in
the same range as that of normal tissues (206). In contrast, some studies
have demonstrated considerably higher activities for many of the glycolytic enzymes of malignant tissues as compared to homologous normal
tissues (239-241). Also, a high-malignancy tumor line grown in tissue
culture was reported to have considerably more activity with regard to
some glycolytic enzymes than did a more normal line of cells (242).
The resolution of this apparent discrepancy between the results of several investigators will be of considerable importance for the eventual
interpretation of the significance of the high rate of glycolysis in cancer
tissue.
d. Several recent studies have been concerned with clarifying the possible role of intracellular factors, such as the level of inorganic phosphate and the levels of ATP and ADP, upon the balance between respiration and glycolysis in the intact cells [(27, 28, 243-248); see also
Section II above]. These investigators indicate a probable critical role of
the concentrations of inorganic phosphate and/or of phosphate ac-