426
ERNEST BUEDING AND EMMANUEL FÄRBER
metabolic pathway, since apparently the integrity of these cells is in
some way dependent on glycolysis (220).
Glycolysis is also very active in blood leucocytes (221-224), but
still undefined is the exact relationship of this metabolic pathway to the
cell integrity of different leucocytes, and to their many functions. In
most instances, the observation of high rates of glycolysis in special
anatomic sites, such as jejunal mucosa, retina, and renal medulla remains interesting but as yet unintegrated into our knowledge of cell
behavior. Recent findings with some tissues in which glycolysis is quantitatively greater than is respiration, such as in cornea or in lens tissue,
have demonstrated the pronounced dependence of the cell integrity on
the respiratory activity even though the latter is very low (225, 226).
It has been known for a long time that the rate of glycolysis is very
high in cells and organs of the developing embryo and that the level of
glycolysis shows interesting variations at different stages of embryologic
growth and differentiation (207, 227). However, despite the relatively
large amount of experimentation in this field, the possible role of
glycolysis in determining and modifying over-all cell function and behavior is not understood.
2. Neoplastic Tissues
One of the most intriguing facts related to the problem of the comparative biochemistry of glycolysis is that malignant tumors, with very
rare exceptions (221, 222), exhibit much higher rates of aerobic and
anaerobic glycolysis than do most normal homologous adult tissues.
Since this was reported by Warburg and co-workers over 30 years ago
(201), it has been confirmed repeatedly in a wide variety of animal and
human malignant tumors (30, 203-206, 208). In fact, a high rate of
aerobic glycolysis can be considered as one of the few metabolic aberrations which have been found consistently to occur in cancer cells.
As with most normal tissues, the rate of glycolysis in tumors is higher
anaerobically than aerobically, i.e., most tumors show a Pasteur effect.
Whether the magnitude of this effect is smaller in tumors than in normal
tissues is difficult to state, since it depends upon the manner of expression. Absolutely, many neoplastic tissues show decreases in the rate of
glycolysis in the presence of oxygen as large or larger than do most
normal tissue. However, since both anaerobic and aerobic glycolysis
rates are elevated, on a percentage basis, the effect usually is considerably less in the neoplastic tissue. Many malignant tumors also show
another interesting relationship between glycolysis and respiration,
namely the Crabtree effect (228). Increasing glucose concentrations in
the medium produce a progressive decrease in the rate of respiration of
ERNEST BUEDING AND EMMANUEL FÄRBER
metabolic pathway, since apparently the integrity of these cells is in
some way dependent on glycolysis (220).
Glycolysis is also very active in blood leucocytes (221-224), but
still undefined is the exact relationship of this metabolic pathway to the
cell integrity of different leucocytes, and to their many functions. In
most instances, the observation of high rates of glycolysis in special
anatomic sites, such as jejunal mucosa, retina, and renal medulla remains interesting but as yet unintegrated into our knowledge of cell
behavior. Recent findings with some tissues in which glycolysis is quantitatively greater than is respiration, such as in cornea or in lens tissue,
have demonstrated the pronounced dependence of the cell integrity on
the respiratory activity even though the latter is very low (225, 226).
It has been known for a long time that the rate of glycolysis is very
high in cells and organs of the developing embryo and that the level of
glycolysis shows interesting variations at different stages of embryologic
growth and differentiation (207, 227). However, despite the relatively
large amount of experimentation in this field, the possible role of
glycolysis in determining and modifying over-all cell function and behavior is not understood.
2. Neoplastic Tissues
One of the most intriguing facts related to the problem of the comparative biochemistry of glycolysis is that malignant tumors, with very
rare exceptions (221, 222), exhibit much higher rates of aerobic and
anaerobic glycolysis than do most normal homologous adult tissues.
Since this was reported by Warburg and co-workers over 30 years ago
(201), it has been confirmed repeatedly in a wide variety of animal and
human malignant tumors (30, 203-206, 208). In fact, a high rate of
aerobic glycolysis can be considered as one of the few metabolic aberrations which have been found consistently to occur in cancer cells.
As with most normal tissues, the rate of glycolysis in tumors is higher
anaerobically than aerobically, i.e., most tumors show a Pasteur effect.
Whether the magnitude of this effect is smaller in tumors than in normal
tissues is difficult to state, since it depends upon the manner of expression. Absolutely, many neoplastic tissues show decreases in the rate of
glycolysis in the presence of oxygen as large or larger than do most
normal tissue. However, since both anaerobic and aerobic glycolysis
rates are elevated, on a percentage basis, the effect usually is considerably less in the neoplastic tissue. Many malignant tumors also show
another interesting relationship between glycolysis and respiration,
namely the Crabtree effect (228). Increasing glucose concentrations in
the medium produce a progressive decrease in the rate of respiration of