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



molecules may penetrate abnormally fast. An alternative explanation is that a hydro- 

 gen-bonding proton-conducting component extends right through the thickness of 

 the membrane. One can readily conceive that such a structure would be selectively 

 permeable to a limited range of hydrogen-bond-forming molecules such as glucose, 

 and also permeable to many small hydrogen-bond-forming molecules. 



(5) The contribution made by enzyme studies 



Various lines of evidence, involving the use both of enzyme poisons and of cyto- 

 chemical methods, have indicated that alkaline phosphatase and cholinesterase, 

 or substances of similar properties, are often concerned in abnormally rapid penetra- 

 tion processes. There are theoretical reasons for treating this information with reserve, 

 for if the structures permitting facilitated diffusion and active transport are hydrogen- 

 bonding proton-conducting components, with structural and stereochemical speci- 

 ficity, we might well expect them to exhibit specific enzymic activity which is inci- 

 dental* and not concerned in the permeation process (Danielli, 1954a and b). But 

 for the purposes of this symposium I shall assume that these enzymes are in fact 

 directly concerned. 



AN ATTEMPT AT A SYNTHESIS 



If the data and considerations presented above are brought together to present a 

 general picture of the plasma membrane we must take into consideration: 



(a) the 'sandwich' structure of the membrane; 



(b) its approximation to a homogeneous lipoid layer; 



(c) that abnormal permeabilities may be explained if in some areas a polar 

 structure extends right through the membrane ; 



(d) that enzymes are present at the sites of transfer, as shown by cytochemical 

 methods; 



(e) that poisons for these same enzymes selectively block transfer; 



(/) some enzymes are known to provide the mechanism whereby chemical energy 

 may be used to activate a contractile protein mechanism; 



(g) to facilitate permeation of polar molecules, hydrogen bonds between the mole- 

 cules and water must be broken : this can be done by supplying protons or alternative 

 hydrogen-bond-forming groups ; 



(h) hydrolytic enzymes, such as phosphatases and esterases, probably work by 

 providing a stereochemically specific hydrogen-bonding proton-conducting surface 

 (just as the non-specific hydrolytic catalysis characteristic of ionic resins and ionic 

 colloidal micelles is probably due to their non-specific proton-conducting surfaces) ; 



(i) so far as can be seen, the specificity for certain molecules, both of enzymes and 

 of transfer processes, must depend upon the same organization of groups in space, 

 both with respect to their nature and their critical spacing and orientation. 



All the above points are provided for if we adopt the hypothesis that facilitated 

 diffusion involves movement through a pore or slit composed of the polar groups of 

 protein lamellae, as in Fig. iB. The junction between two protein lamellae will not 

 be a simple aqueous pore: it will be a region composed of polar groups and including 



* Just as the esterase activity of certain peptidases is probably incidental. 



II 



