168
ERNEST SCHOFFENIELS
diuretic hormone on the net flux of Na and water across the isolated toad
bladder. The authors postulate an indirect action by formation of an
intermediary cyclic adenylic acid (3',5'-AMP). In this hypothesis, 3',5'AMP, would act on the passive permeability to Na and to water.
Another possibility would be that, besides being actively transported,
the amino acid acts directly and independently on the passive permeability characteristics of the membrane in the manner of certain quaternary ammonium derivatives (see Section III).
Finally it may be proposed that the amino acid being catabolized in
the cell, it increases the amount of ATP available for the active transport
of the inorganic ions directly involved in the generation of the potential
difference.
If we now turn to the effect of cations on the active transport of
glucose, amino acids, or fatty acids, it has been proposed that they would
have a direct action on the movement of the carrier for the organic
molecules (46). In this hypothesis, amino acid uptake, for instance,
could be wholly driven by the energy inherent in the asymmetry of
cellular alkali metal distribution (117).
Another possibility, however, is that the cationic content of the cell
sets the rate of the transport of organic ions and molecules by direct
action on the enzyme systems involved in the process. We favor this
view because, as we will show later (Section V), there is experimental
evidence in favor of the idea that the rate of synthesis as well as the
breakdown of amino acids is directly dependent on the intracellular
content in Na and K. We also know that an enzyme system, a microsomal
adenosine triphosphatase, requires very well-defined amounts of Na
and Κ for optimal activity (118).
We may summarize the results by saying that in epithelia without
enough endogenous substrate, e.g., the small intestine epithelium, the
active transport of cations needs an external source of substrate for
optimal activity. Increase in the potential difference is a consequence of
the activation of the cation "pump." On the other hand, active transport
of glucose, amino acids, or fatty acids is possible only in the presence of
a saline having a well-defined ionic composition, as the enzyme systems
involved in the transport mechanisms have well-defined requirements
in cations.
V. Some Aspects of the Regulation of the Intracellular Pool of
Free Amino Acids
Besides their well-known roles and functions in the general metabolism of an organism (development, neurosecretion, amino donors, trans-
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