DANIELLI 



Active transport involves the movement of molecules by forces additional to those of 

 thermal agitation. The result of active transport may (if the free-energy change of 

 the active process is ignored) be an increase in free energy of the system, and an 

 increase in chemical potential gradients. 



Of these three processes we know least about active transport, and most about 

 diffusion. As we learn more about the nature of active transport, it may prove that a 

 number of distinct types of process are involved which can be defined separately, just 

 as it has recently proved possible to separate facilitated diffusion from active transport. 



CLASSIFICATION OF TECHNIQUES 



A variety of techniques may be employed to differentiate between diffusion, facili- 

 tated diffusion and active transport, and to approach the mechanisms underlying 

 individual processes of facilitated diffusion and active transport. These techniques 

 can be roughly divided into six groups. 



( i ) Morphological studies. The examination of the structure and ultrastructure of 

 secretory organs and cells is of outstanding importance, and too frequently under- 

 rated. In many cases the limits of analysis using the light-microscope are far from 

 exhausted. The exploitation of electron-microscope studies should be of the greatest 

 value, as is suggested by the recent publication of Sjostrand's (1953) work on the 

 free and other cell borders, nuclear membranes and mitochondrial membranes of 

 kidney proximal tubule cells. It is probable that a full understanding of the details 

 revealed by electron-microscopy must await the development of cytochemical 

 methods for use with electron-microscopy, but even to have available the structural 

 detail, without chemical detail, of the membranes concerned will be highly stimulat- 

 ing. 



(2) Kinetic studies. The examination of the rates of penetration of substances 

 through membranes, and of the effect of variation in concentration, temperature, 

 ionic strength and other environmental conditions on these rates, are included in 

 this heading. Included also is the effect of variation in molecular structure and stereo- 

 chemistry, and the use of isotopes. Isotopes are particularly useful in the determina- 

 tion of total transfer, as opposed to net transfer. 



(3) Metabolic studies. Although studies of metabolism are unlikely to yield much 

 useful information about the actual mechanism of transfer, they are often useful in 

 showing that transfer is in some way dependent on metabolism. This permits distinc- 

 tion between diffusion on the one hand, and facilitated diffusion and active transfer 

 on the other. It does not necessarily permit distinction between facilitated diffusion 

 and active transfer, since in the former case, although no energy contribution is 

 required from the cell for transfer, energy may be required to maintain the membrane 

 in an active state permitting facilitated diffusion. The effect of metabolism is usually 

 best studied by depriving the cells of metabolites (e.g. glucose) or by use of poisons 

 (e.g. cyanide, dinitrophenol). 



(4) Cytochemical studies. These are at present sharply limited by the lack of a suffici- 

 ent variety of reliable cytochemical techniques. A few observations of major import- 

 ance have been made, including: (a) the high concentration of alkaline phosphatase 

 at the secretory surfaces of many secretory cells (Danielli, 1953); (b) the high 



