192
ERNEST SCHOFFENIELS
An ATPase activity has indeed been ascribed to various cell membranes (214-217); more recently an ATPase activity sensitive to alkali
metal ions, first isolated by Skou in 1957 (118) from crab nerves, has
been demonstrated in many other cells
(218-224).
These findings do not necessarily demonstrate that the ATPase isolated is the molecule directly responsible for the transfer of material
across the membrane. Since ATP is generally assumed to be the important source of cellular energy, there must be various ATPases affected
differently by the intracellular conditions in order to provide, in the
right sequence, the energy required by all the anabolic functions of the
cell. One possibility still remains to be considered in the more specific
case of alkali metal ions transport: ATP being the energy source, the
membrane ATPase sensitive to the cation concentration of both intracellular and extracellular liquids catalyzes the transfer of a high-energy
bond to the molecular architecture more directly related to the handling
of ions across the membrane. This would give the cell additional control
of the cation content of the intracellular fluid.
Another important aspect of the problem to be considered is the
nature of the intimate mechanism used by the cell in the transfer of
ions or molecules across the barrier. Are we dealing with a shuttling
carrier, or is the solute moving along sites on a fixed structure?
It is actually very difficult to answer this question. Many models
have been proposed [see for instance (225)]. They are discussed adequately in the very important review written by Christensen
(226).
When dealing with this problem, however, one has the impression that
the only thing to be challenged is the imagination of the writer: any
model thermodynamically possible is indeed acceptable since we do not
have any experimental argument favoring one specific model more than
another.
So far the active sites have been studied along two principal lines of
investigation:
(a) The behavior of analogs of the solute is studied on the intact cell
to find the structural modification which abolishes the transport. The
chemical function responsible for the effect observed can sometimes be
identified by examining the structure of the various compounds known
to affect in the same way the permeability characteristics of the membrane (48, 100-102, 106, 107, 109, 110, 175, 194). On the basis of molecular complementarity a mirror image of the substrate can be proposed,
thus giving the possible nature and configuration of the active site(s)
on the molecule. This method has been used successfully in enzyme
chemistry (227-230) and has tentatively been applied to resolve some
problems on membrane permeability (231).
ERNEST SCHOFFENIELS
An ATPase activity has indeed been ascribed to various cell membranes (214-217); more recently an ATPase activity sensitive to alkali
metal ions, first isolated by Skou in 1957 (118) from crab nerves, has
been demonstrated in many other cells
(218-224).
These findings do not necessarily demonstrate that the ATPase isolated is the molecule directly responsible for the transfer of material
across the membrane. Since ATP is generally assumed to be the important source of cellular energy, there must be various ATPases affected
differently by the intracellular conditions in order to provide, in the
right sequence, the energy required by all the anabolic functions of the
cell. One possibility still remains to be considered in the more specific
case of alkali metal ions transport: ATP being the energy source, the
membrane ATPase sensitive to the cation concentration of both intracellular and extracellular liquids catalyzes the transfer of a high-energy
bond to the molecular architecture more directly related to the handling
of ions across the membrane. This would give the cell additional control
of the cation content of the intracellular fluid.
Another important aspect of the problem to be considered is the
nature of the intimate mechanism used by the cell in the transfer of
ions or molecules across the barrier. Are we dealing with a shuttling
carrier, or is the solute moving along sites on a fixed structure?
It is actually very difficult to answer this question. Many models
have been proposed [see for instance (225)]. They are discussed adequately in the very important review written by Christensen
(226).
When dealing with this problem, however, one has the impression that
the only thing to be challenged is the imagination of the writer: any
model thermodynamically possible is indeed acceptable since we do not
have any experimental argument favoring one specific model more than
another.
So far the active sites have been studied along two principal lines of
investigation:
(a) The behavior of analogs of the solute is studied on the intact cell
to find the structural modification which abolishes the transport. The
chemical function responsible for the effect observed can sometimes be
identified by examining the structure of the various compounds known
to affect in the same way the permeability characteristics of the membrane (48, 100-102, 106, 107, 109, 110, 175, 194). On the basis of molecular complementarity a mirror image of the substrate can be proposed,
thus giving the possible nature and configuration of the active site(s)
on the molecule. This method has been used successfully in enzyme
chemistry (227-230) and has tentatively been applied to resolve some
problems on membrane permeability (231).