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
257
K
O n the whole there has been a tendency to concentrate on the role of
aerobic pathways in essential metabolic processes and to regard
glycolysis as a primitive and less essential energy-yielding pathway. A
more specific requirement for some of the reactions of glycolysis may
be implied by the fact that oxamate is lethal to HeLa cells (Papaconstantinou and Colowick, 1961a, b) and 2-deoxyglucose inhibits
growth (Barban, 1961). On the other hand some cell-lines will grow in a
medium containing ribose and pyruvate but no glucose (Eagle et al.,
1958).
These considerations bring us back to the general question of the
relationships between aerobic pathways and specialized functions on
the one hand and glycolysis and undifferentiated growth on the other.
A clearcut answer can now be given to one part of this question.
Rapidly growing cells, whose only functions are replication of their
own substance and cell division, can exist in relatively anaerobic conditions and, in special circumstances, may even be able to grow completely anaerobically.
The other part of the question probably cannot be covered by a general answer. Certain processes demand intact electron-transfer pathways
with a hydrogen acceptor, almost invariably oxygen. For instance the
synthesis of many mucopolysaccharides requires the formation of
glucuronic acid from glucose and this requires an oxidative mechanism
since the reduction of pyruvate to lactate can account only for the
electrons made available in the formation of pyruvate from glucose by
glycolysis. Consequently the normal functioning of specialized cells
producing acid mucopolysaccharides must as a rule require oxygen.
The synthesis of many other special molecules is governed by the same
consideration. Moreover, in addition to these qualitative requirements
it is possible that in some circumstances there may be a quantitative
requirement for oxidative metabolism. This arises from the fact that
aerobic pathways produce fifteen to sixteen times as much A T P from a
given amount of glucose as glycolysis. Consequently if in performing its
specialized functions a cell has a very high requirement for A T P it may
not be able to obtain sufficient energy from glycolysis alone unless it
has an exceptionally high glycolytic capacity. This may be the reason
why heart explants cease to beat when they are treated with inhibitors
of the Krebs cycle such as fluoroacetate, although they nevertheless
continue to survive (Allsopp and Fell, 1950).
In summary, then, it is reasonable to predict that many specialized
cells will have a requirement for aerobic pathways. Unspecialized cells,
on the other hand, may be able to grow reasonably well at low oxygen
tensions if they are provided with a complete medium. Otherwise they
must be supplied with oxygen also.
257
K
O n the whole there has been a tendency to concentrate on the role of
aerobic pathways in essential metabolic processes and to regard
glycolysis as a primitive and less essential energy-yielding pathway. A
more specific requirement for some of the reactions of glycolysis may
be implied by the fact that oxamate is lethal to HeLa cells (Papaconstantinou and Colowick, 1961a, b) and 2-deoxyglucose inhibits
growth (Barban, 1961). On the other hand some cell-lines will grow in a
medium containing ribose and pyruvate but no glucose (Eagle et al.,
1958).
These considerations bring us back to the general question of the
relationships between aerobic pathways and specialized functions on
the one hand and glycolysis and undifferentiated growth on the other.
A clearcut answer can now be given to one part of this question.
Rapidly growing cells, whose only functions are replication of their
own substance and cell division, can exist in relatively anaerobic conditions and, in special circumstances, may even be able to grow completely anaerobically.
The other part of the question probably cannot be covered by a general answer. Certain processes demand intact electron-transfer pathways
with a hydrogen acceptor, almost invariably oxygen. For instance the
synthesis of many mucopolysaccharides requires the formation of
glucuronic acid from glucose and this requires an oxidative mechanism
since the reduction of pyruvate to lactate can account only for the
electrons made available in the formation of pyruvate from glucose by
glycolysis. Consequently the normal functioning of specialized cells
producing acid mucopolysaccharides must as a rule require oxygen.
The synthesis of many other special molecules is governed by the same
consideration. Moreover, in addition to these qualitative requirements
it is possible that in some circumstances there may be a quantitative
requirement for oxidative metabolism. This arises from the fact that
aerobic pathways produce fifteen to sixteen times as much A T P from a
given amount of glucose as glycolysis. Consequently if in performing its
specialized functions a cell has a very high requirement for A T P it may
not be able to obtain sufficient energy from glycolysis alone unless it
has an exceptionally high glycolytic capacity. This may be the reason
why heart explants cease to beat when they are treated with inhibitors
of the Krebs cycle such as fluoroacetate, although they nevertheless
continue to survive (Allsopp and Fell, 1950).
In summary, then, it is reasonable to predict that many specialized
cells will have a requirement for aerobic pathways. Unspecialized cells,
on the other hand, may be able to grow reasonably well at low oxygen
tensions if they are provided with a complete medium. Otherwise they
must be supplied with oxygen also.