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
263
required by both. It may not be profitable to speculate on the precise
nature of the limiting metabolite because, as has been indicated,
different substances may be involved at different times and in different
circumstances. For instance a popular explanation for the Pasteur
effect is that A D P or iP (inorganic phosphate) or both are limited in
amount. Hence, a decrease in any ADP-requiring pathway may
permit an increase in another. This theory presupposes that the amounts
of A D P or iP are limiting at all times. However, since there is evidence
that stationary cell populations are producing much more energy than
they require this suggests that a variable degree of "uncoupling" can
readily occur. Therefore, although this objection does not exclude the
operation of the above mechanism it does mean that it should be
accepted with caution. Other limiting substances, such as reduced
nicotinamide-adenine dinucleotides, have been proposed and an
equally good case can be made out for them. Almost all ideas are,
however, based on that of competition between the aerobic and anaerobic pathways and the evidence from cell-culture experiments would
bear them out (Paul, 1961; Wu, 1959).
2. "Coupling" and "Uncoupling"
Certain substances, such as 2:4-dinitrophenol, can induce a great
increase in respiration above the normal level (De Bruyn, 1959; Siegel
and Cailleau, 1956). It is thought that normally the respiratory rate is
limited by the availability of A D P and iP for oxidative phosphorylation.
Uncoupling agents are considered to release "ATPase-like" activity
which results in the breakdown of A T P as soon as it is formed, with the
release of A D P and iP for further phosphorylation. The overall result
of uncoupling, therefore, is greatly to decrease the efficiency of the
whole system. The phenomenon of uncoupling itself implies that
normally these reactions are coupled. However the actual degree of
coupling would seem to vary because, as has been pointed out, there is
little difference between the respiration of rapidly growing and
stationary cultures although the energy requirements of the latter are
almost certainly very much less.
3. Enzymic Adaptation
The positive existence of adaptive enzymes in cultured animal cells
has been proved only very recently and it is probably too early to
speculate about the parts they play in specific metabolic pathways. It
is, however, appropriate to mention that one or two enzymes involved in
carbohydrate metabolism appear to behave in this manner. Among the
most interesting are malic dehydrogenase which we have found to
decrease if cells are grown in conditions of low oxygen tension (Paul
263
required by both. It may not be profitable to speculate on the precise
nature of the limiting metabolite because, as has been indicated,
different substances may be involved at different times and in different
circumstances. For instance a popular explanation for the Pasteur
effect is that A D P or iP (inorganic phosphate) or both are limited in
amount. Hence, a decrease in any ADP-requiring pathway may
permit an increase in another. This theory presupposes that the amounts
of A D P or iP are limiting at all times. However, since there is evidence
that stationary cell populations are producing much more energy than
they require this suggests that a variable degree of "uncoupling" can
readily occur. Therefore, although this objection does not exclude the
operation of the above mechanism it does mean that it should be
accepted with caution. Other limiting substances, such as reduced
nicotinamide-adenine dinucleotides, have been proposed and an
equally good case can be made out for them. Almost all ideas are,
however, based on that of competition between the aerobic and anaerobic pathways and the evidence from cell-culture experiments would
bear them out (Paul, 1961; Wu, 1959).
2. "Coupling" and "Uncoupling"
Certain substances, such as 2:4-dinitrophenol, can induce a great
increase in respiration above the normal level (De Bruyn, 1959; Siegel
and Cailleau, 1956). It is thought that normally the respiratory rate is
limited by the availability of A D P and iP for oxidative phosphorylation.
Uncoupling agents are considered to release "ATPase-like" activity
which results in the breakdown of A T P as soon as it is formed, with the
release of A D P and iP for further phosphorylation. The overall result
of uncoupling, therefore, is greatly to decrease the efficiency of the
whole system. The phenomenon of uncoupling itself implies that
normally these reactions are coupled. However the actual degree of
coupling would seem to vary because, as has been pointed out, there is
little difference between the respiration of rapidly growing and
stationary cultures although the energy requirements of the latter are
almost certainly very much less.
3. Enzymic Adaptation
The positive existence of adaptive enzymes in cultured animal cells
has been proved only very recently and it is probably too early to
speculate about the parts they play in specific metabolic pathways. It
is, however, appropriate to mention that one or two enzymes involved in
carbohydrate metabolism appear to behave in this manner. Among the
most interesting are malic dehydrogenase which we have found to
decrease if cells are grown in conditions of low oxygen tension (Paul