The present position in the field of facilitated diffusion and selective active transport 



The removal of both compounds has a 'half-life' of about four minutes. The speed 

 with which insulin can be removed suggests that its action must be upon the external 

 surface of the plasma membrane. The alternative hypothesis, that there is a very 

 rapid interchange of insulin across the plasma membrane, whilst not utterly impos- 

 sible, is highly improbable. 



It has been suggested (Cori, 1945) that these hormones act upon hexokinase, and 

 that penetration is a phosphorylative transfer catalysed by hexokinase. The above 

 results are not readily explicable on this hypothesis. 



The penetration of glucose into muscle cells is commonly described as active 

 transfer. However, there is no evidence that movement of glucose into muscle cells 

 ever occurs against a concentration gradient. The simplest hypothesis compatible 

 with the observations recorded to date is that glucose enters muscle cells by facilitated 

 diffusion, that it is phosphorylated after entry so that a concentration gradient 

 favouring entry is maintained, and that the action of insulin is exerted from the cell 

 exterior upon the mechanism of facilitated diffusion. 



(B) Penetration into human red cells 



Most non-electrolytes enter red cells by simple diffusion, but there are a number 

 of exceptions to this rule. Urea enters many red cells abnormally fast — probably by 

 facilitated diffusion: the same is true of glycerol for the red cells of many rodents and 

 primates, and of glucose for the red cells of primates. Glycerol penetrates about io 2 

 times faster into human red cells than is calculated should be the case for simple 

 diffusion, and as is found experimentally for many cells, including cattle, sheep and 

 pig red cells. Glucose penetrates about io 4 times faster than is calculated. But neither 

 of these substances is caused to move against a concentration gradient. These sub- 

 stances penetrate at a 'normal' speed through most of the cell surface, and abnormally 

 fast through a small fraction of the surface (Danielli, 1943). These small active 

 patches are often readily poisoned — e.g. by copper ions (Jacobs and Corson, 1934). 

 When the active patches are poisoned, the rate of penetration falls to that calculated 

 for diffusion. Davson (1954) has recently suggested that the high rate of penetration 

 found with anions is also a case of facilitated diffusion. 



On the other hand, several investigators, particularly Maizels ( 1 954) , have shown 

 that K + and Na+ may move into and out of red cells by active processes, against 

 concentration gradients. Deprivation of glucose stops the active process and move- 

 ment of ions then occurs, by diffusion, down the concentration gradients. 



Table II sets out some of the results which have been obtained with enzyme 

 poisons on the movements of glucose, glycerol, sodium and potassium with human 

 red cells. Copper ions and bromacetophenone strongly inhibit facilitated diffusion 

 of both glycerol and glucose, whereas iodoacetate does not. These results suggest that 

 there may be SH groups concerned, but relatively unreactive SH groups since iodo- 

 acetate is ineffective. But dinitrofluorobenzene, although a very powerful inhibitor 

 of facilitated diffusion of glucose, does not inhibit glycerol movement. This is com- 

 patible with involvement of SH groups in the case of glucose, but not in the case of 

 glycerol. Diazonium hydroxides have no effect with either glycerol or glucose, so 

 that it is possible that neither tyrosine, histidine or tryptophane are involved. The 

 inactivity of iodoacetate, cyanide and dinitrophenol shows that respiration, glycolysis 



