AUGUST 19, 1921 alsberg: physiological chemistry 333 



which penetrates into the cells, is precipitated by the tannic acid. The 

 formation of these precipitates may be obser\^ed under the microscope. 

 The alkaloid being removed by precipitation, more alkaloid diffuses in 

 until all the available tannic acid has been consumed. The alkaloid 

 enters because the cell-membrane is permeable to it. Whether this 

 permeability is due to lipoid solubility of the alkaloid, surface effect, or 

 adsorption need not concern us now. Were there no tannin within the 

 cell, only so much alkaloid would diffuse into it as is required to es- 

 tablish equilibrium between the interior of the cell and the medium 

 bathing the cell. More, however, passes in because a part is combined 

 firmly with the tannin. By such a chemical mechanism, as well as in 

 the other ways above discussed, substances may accumulate in special 

 organs or cells. ^^ 



The indifferent narcotics are substances that are not dissociated. 

 The majority of the substances which readily permeate cells are not 

 ionized. This is beautifully illustrated by the difference in the action 

 of the free alkaloid bases and their salts, as shown by Overton. The 

 former are more poisonous than the latter, at least to the individual 

 cell. The free base alone is able to pass through the cell-membrane. 

 In a solution of the base all of it is free to pass through the membrane. 

 The solution of the salt only contains free base to the extent that 

 the salt is dissociated. With a base as weak as the alkaloids united 

 with the common very powerful acids, the amount of dissociation will 

 be very slight. The action of the salt is therefore slower than that of 

 the free base. 



Analogous conditions seem to prevail in the case of inorganic salts. 

 As a rule ions do not pass through cell-membrane and it is very doubt- 

 ful whether the ordinary salts of the organism, most of which plas- 

 molyze, enter cells as ions.'^' Certain inorganic salts, however, 



'* For other mechanisms, see W. SchulEmann, Die vitale Fdrhung in ihrer Bedeutung 

 fiir Anatomie, Physiologic, Pathologie und Pharmakologie. Biochem. Zeitschr. 80: 1. 1917. 



^ Apparently the fact that the lipoids, as shown by Thudichum, readily form colloidal 

 solutions in water, has been overlooked by those who have speculated on the subject. Koch 

 has shown that such solutions change the solubility of inorganic salts and render them 

 soluble with the lipoid in ether. I myself have observed that if a solution of egg yolk in 

 10 per cent NaCl be extracted with ether a small amount of material giving the biuret re- 

 action passes into the ether. A thorough study of the manner in which lipoids and proteins 

 modify the solubility of such substances as glucose, amino-acids, and inorganic salts is 

 needed. It may well be that it will furnish the key to the mechanism by which such 

 food-stuffs enter cells. However, it should also be kept in mind that none of the hypotheses 

 concerning the character of cell-membranes is capable of explaining completely the entrance 

 into cells of all substances that undoubtedly get into them. I have been careful to 



