7. C A R B O H Y D R A T E A N D E N E R G Y M E T A B O L I S M
251
particularly favourable to cells with a high glycolytic capacity. The
aerobic (pentose-phosphate shunt and Krebs cycle) pathways are
presumably necessary for certain synthetic reactions in specialized cells
where they provide pools of small molecules for the synthesis of a variety
of components. O n the other hand Quastel and Bickis (1959) found
that in tumour and embryonic cells the glycolytic pathway was at least
as efficient a source of energy for protein synthesis as the aerobic pathways. Bonting and Jones (1954) also observed that protein synthesis
continued at a high level in lung and intestine tissue cultured under
nitrogen. Hence, although specialized functions may be rather dependent on aerobic conditions, cells performing the most basic functions
involved in replication may be able to survive in conditions of relatively
low oxygen tension. This may result in the selection of cells which are
capable of rapid multiplication in partially anaerobic conditions such
as are often encountered in cultures. Cells capable of producing large
amounts of energy from glycolysis might reasonably be expected to
survive better in these conditions, and it is indisputable that most
established cell cultures possess a high glycolytic capacity (Burk, Hunter
and Woods, 1954; Burk and Woods, 1956; Halevy and Avivi, 1958;
Paul, 1959; Suschny et al., 1958; Woods, Sanford, Burk and Earle,
1959; Wu, 1959).
It may be mentioned at this point that when glucose utilization and
lactic acid production in cell cultures are carefully measured, a paradoxical situation is sometimes encountered since it is not infrequently
found that the lactic acid formed is in excess of the amount that could
have arisen from the glucose consumed. The probable reason is that
pyruvic acid can arise by spontaneous decarboxylation of oxaloacetic
acid and hence lactic acid can be directly derived from products of the
Krebs cycle. Consequently lactic acid can arise from the metabolism of
certain amino acids as well as from glucose.
It is frequently implied and often stated that glycolysis and respiration tend to vary inversely. In certain circumstances this is, of course,
true. Thus the elimination of respiration by imposing anaerobic conditions may result in increased glycolysis (Pasteur effect) and conversely
augmentation of glycolysis by increasing the glucose concentration in
the medium may inhibit respiration (Crabtree effect). These are,
however, freely reversible effects, probably dependent on limitation of
co-factors competed for by the two pathways and they have nothing to
do directly with the constitutional level of glycolysis or respiration in
any given cell. It is implicit in Warburg's theory of carcinogenesis that
cells with a high glycolytic capacity also have impaired respiration.
This association is sometimes found in freshly isolated tumour tissue but
it does not apply generally and it is erroneous to consider that it applies
251
particularly favourable to cells with a high glycolytic capacity. The
aerobic (pentose-phosphate shunt and Krebs cycle) pathways are
presumably necessary for certain synthetic reactions in specialized cells
where they provide pools of small molecules for the synthesis of a variety
of components. O n the other hand Quastel and Bickis (1959) found
that in tumour and embryonic cells the glycolytic pathway was at least
as efficient a source of energy for protein synthesis as the aerobic pathways. Bonting and Jones (1954) also observed that protein synthesis
continued at a high level in lung and intestine tissue cultured under
nitrogen. Hence, although specialized functions may be rather dependent on aerobic conditions, cells performing the most basic functions
involved in replication may be able to survive in conditions of relatively
low oxygen tension. This may result in the selection of cells which are
capable of rapid multiplication in partially anaerobic conditions such
as are often encountered in cultures. Cells capable of producing large
amounts of energy from glycolysis might reasonably be expected to
survive better in these conditions, and it is indisputable that most
established cell cultures possess a high glycolytic capacity (Burk, Hunter
and Woods, 1954; Burk and Woods, 1956; Halevy and Avivi, 1958;
Paul, 1959; Suschny et al., 1958; Woods, Sanford, Burk and Earle,
1959; Wu, 1959).
It may be mentioned at this point that when glucose utilization and
lactic acid production in cell cultures are carefully measured, a paradoxical situation is sometimes encountered since it is not infrequently
found that the lactic acid formed is in excess of the amount that could
have arisen from the glucose consumed. The probable reason is that
pyruvic acid can arise by spontaneous decarboxylation of oxaloacetic
acid and hence lactic acid can be directly derived from products of the
Krebs cycle. Consequently lactic acid can arise from the metabolism of
certain amino acids as well as from glucose.
It is frequently implied and often stated that glycolysis and respiration tend to vary inversely. In certain circumstances this is, of course,
true. Thus the elimination of respiration by imposing anaerobic conditions may result in increased glycolysis (Pasteur effect) and conversely
augmentation of glycolysis by increasing the glucose concentration in
the medium may inhibit respiration (Crabtree effect). These are,
however, freely reversible effects, probably dependent on limitation of
co-factors competed for by the two pathways and they have nothing to
do directly with the constitutional level of glycolysis or respiration in
any given cell. It is implicit in Warburg's theory of carcinogenesis that
cells with a high glycolytic capacity also have impaired respiration.
This association is sometimes found in freshly isolated tumour tissue but
it does not apply generally and it is erroneous to consider that it applies