CONCEPTS AND TERMS 



fields of the membrane, or even from single, well-placed, charged 

 groups at channels that might otherwise serve for passage. 



The evidence for a lipid harrier comes from a tendency of 

 classes of small molecules to enter cells with rates more or less di- 

 rectly related to their degree of lipophilic nature, as revealed, for 

 example, by their oil-water distribution coefficients (Overton, 1899, 

 1902). Classic results supporting Overton's hypothesis are shown in 

 Figure 4. These observations were made by Collander (1937) on the 

 plant cell, Chdra. 



The presence of a lipid barrier means that we cannot predict 

 which molecules will pass the barrier— nor how rapidly they will 

 pass— from their size and shape alone; we must also consider their 

 polarity. As indicated a few paragraphs above, biologists hoped for 

 many years that consideration of the factors of size, shape, charge, 

 and polarity alone would serve to account for the full range of the 

 movement of molecules. One should consult the writings of Oster- 

 hout (e.g., in 1933) for vigorous representations of this important 

 point of view. We must continue to keep in mind the peculiarities 

 of distribution that can be produced across a nonaqueous barrier. 



Mediation of transport 



Facilitated diffusion. Many molecules, especially hydrophilic 

 ones, show peculiarities in their migration through the plasma mem- 

 brane, even though this may be downhill, i.e., in the direction of 

 the concentration gradient. These peculiarities indicate that simple 

 diffusion of the free migrating molecule cannot be the rate-limiting 

 step. These are also generally the solutes that would not be expected 

 to enter a lipid phase readily and which would require either an 

 interruption of the lipid barrier or a modification of their physical 

 properties to permit them to enter it. 



For example, in 1925 Ege and associates noticed that the time 

 for glucose to come to equilibrium across the human red blood cell 

 from a 5.5 per cent solution of glucose increased from about 20 

 minutes to 3 or 4 hours when the temperature was lowered from 40 

 to 30°. Masing had already interpreted similar temperature effects 

 with remarkable insight in 1914. But more significantly, the time 

 to reach equilibrium at 30° fell to less than 1 minute when a 0.2 

 per cent solution of glucose in saline was used instead. Unfortu- 



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