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J O H N P A U L
as the temperature is increased, whereas growth is usually maximum
at a temperature of 35-36° and falls off above and below the optimum.
Non-specific effects of serum and other components on carbohydrate
metabolism have at times been reported (S. Kuwabara, 1959; Phillips
and Andrews, 1960; Wu, 1959) but it is extremely difficult to separate
these from some of the effects which have already been described, and no
detailed study has yet been made of them.
B. R E G U L A T I N G M E C H A N I S M S
Much of the interest in the phenomena exhibited by cultured cells
arises from their bearing on the mechanisms controlling carbohydrate
metabolism. For many years the Pasteur effect, in particular, has
excited a good deal of speculation and although they shed no new light
on this problem it is interesting to consider how tissue culture observations fit in with existing speculations.
1. Control by Limitation of Metabolites
Conditions frequently arise in which the limiting factor in the
catabolism of carbohydrate is the availability of a particular metabolite.
One rather special example has already been mentioned—the limitation
of respiration due to oxaloacetate depletion in the absence of carbon
dioxide. Failure of growth in the absence of oxygen or glucose can be
ascribed to the same general cause. In the usual experimental conditions care is taken to provide all the necessary metabolites in excess
in the medium but the availability of carbohydrate for metabolism may
nevertheless be limiting due to permeability barriers or rate-limiting
enzymes (Wu, 1959). Indeed, it seems quite likely that the rate of
carbohydrate metabolism, in conditions which are otherwise nonlimiting, may be dependent on just these factors. For instance Eagle et
al. (1958) showed that although galactose and fructose could substitute
for glucose they were not quantitatively equivalent and the ease with
which they were utilized was proportional to the hexokinase activity
for each sugar. Several workers have reported that the rate of glucose
utilization and the glycolytic capacity of any given cell are directly
related to the hexokinase activity for that cell (Warburg et al., 1958;
Wu, 1959). Hence it seems a reasonable proposition that in most
instances the primary factor controlling the catabolism of carbohydrate
is the hexokinase or other system permitting entry of monosaccharides
to the appropriate metabolic pathways. The subsequent fate of the
sugar may depend on several controlling factors but the Pasteur and
Crabtree effects seem to indicate that there is a reciprocity between
aerobic pathways and glycolysis. The observations suggest that there is
some competition by these pathways for a metabolite (or metabolites)
J O H N P A U L
as the temperature is increased, whereas growth is usually maximum
at a temperature of 35-36° and falls off above and below the optimum.
Non-specific effects of serum and other components on carbohydrate
metabolism have at times been reported (S. Kuwabara, 1959; Phillips
and Andrews, 1960; Wu, 1959) but it is extremely difficult to separate
these from some of the effects which have already been described, and no
detailed study has yet been made of them.
B. R E G U L A T I N G M E C H A N I S M S
Much of the interest in the phenomena exhibited by cultured cells
arises from their bearing on the mechanisms controlling carbohydrate
metabolism. For many years the Pasteur effect, in particular, has
excited a good deal of speculation and although they shed no new light
on this problem it is interesting to consider how tissue culture observations fit in with existing speculations.
1. Control by Limitation of Metabolites
Conditions frequently arise in which the limiting factor in the
catabolism of carbohydrate is the availability of a particular metabolite.
One rather special example has already been mentioned—the limitation
of respiration due to oxaloacetate depletion in the absence of carbon
dioxide. Failure of growth in the absence of oxygen or glucose can be
ascribed to the same general cause. In the usual experimental conditions care is taken to provide all the necessary metabolites in excess
in the medium but the availability of carbohydrate for metabolism may
nevertheless be limiting due to permeability barriers or rate-limiting
enzymes (Wu, 1959). Indeed, it seems quite likely that the rate of
carbohydrate metabolism, in conditions which are otherwise nonlimiting, may be dependent on just these factors. For instance Eagle et
al. (1958) showed that although galactose and fructose could substitute
for glucose they were not quantitatively equivalent and the ease with
which they were utilized was proportional to the hexokinase activity
for each sugar. Several workers have reported that the rate of glucose
utilization and the glycolytic capacity of any given cell are directly
related to the hexokinase activity for that cell (Warburg et al., 1958;
Wu, 1959). Hence it seems a reasonable proposition that in most
instances the primary factor controlling the catabolism of carbohydrate
is the hexokinase or other system permitting entry of monosaccharides
to the appropriate metabolic pathways. The subsequent fate of the
sugar may depend on several controlling factors but the Pasteur and
Crabtree effects seem to indicate that there is a reciprocity between
aerobic pathways and glycolysis. The observations suggest that there is
some competition by these pathways for a metabolite (or metabolites)