CONCEPTS AND TERMS 



and that the supply of this structure comes to limit the transport 

 rate at the higher concentrations. This structure or group is said 

 to mediate the transport, and we thus have a mediated transport. 

 If the transport is not able to proceed in an uphill direction, the 

 mediation is a passive one, and we have what Daniclli called facili- 

 tated diffusion. 



Addition of a solute analog may serve better than an excess of 

 the solute itself to demonstrate the limitation in the supply of the 

 mediating structure. Figure 5 shows how inhibition by hypoxanthine 

 served to demonstrate that most but not all of the migration of uric 

 acid into the human red blood cell is mediated (Overgaard-Hansen 

 and Lassen, 1959; cf. Lassen, 1961). [This result was obtained in 

 0.11 M phosphate medium. In Ringer solution no diffusion com- 

 ponent is recognized (Lassen, 1961).] 



If solutes diffuse through pores that are small enough, in rela- 

 tion to the size of the solute molecules, restricted diffusion may 

 occur. In this phenomenon, the migration rate may cease to in- 

 crease linearly with concentration, as more and more collisions oc- 

 cur unfavorable to passage through the pores (cf. Zierler, 1961). 

 This phenomenon should be distinguishable from chemical media- 

 tion of transport by the following characteristics: 



1. The analogs that most effectively inhibit the migration of a 

 solute will themselves not pass as easily by restricted diffusion, 

 whereas in mediated transport they will be transported more rapidly. 



2. A flux in one direction would tend to be depressed by a 

 flux in the other in restricted diffusion. We shall see below that the 

 opposite effect has been observed for mediated transport. 



3. One could hardly expect a significant difference in the 

 passage of d and l isomers (e.g., d- and L-alanine) by restricted dif- 

 fusion. 



If no limits to the linear relationship between concentration 

 and migration rates can be found, diffusion is still not proved to be 

 the mode of transfer, since the capacity for mediation may be ex- 

 tremely high, either because the site is very abundant or because 

 it functions very quickly. Even the very rapid entry of chloride 

 into the red blood cell may be partially mediated (Tosteson, 1959). 



How mediation can occur. To illustrate what is probably the 

 simplest possible explanation, we shall choose a facilitated diffusion— 

 the entry of glycerol into the human red blood cell. The erythro- 

 cytes of most other species admit glycerol only very slowly. As a 



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