Biophysical Factors in Drug Action 27 



The fact that the whole cuticle becomes eventually deeply tanned 

 and hardened by prolonged treatment with />-benzoquinone 

 indicates the general lipo-protein character of the cuticle struc- 

 ture. We may conclude that the spatial changes produced by a 

 fat solvent or narcotic in the mosaic organization are as shown 

 in figures 4a, 4h. There is a general swelling and increase in 

 phase volume of the lipophilic radially arranged aggregates, 

 resulting in an increase in the permeability of this phase to fat 

 solvents which have less lipid-dispersant properties, such as 

 ethyl alcohol. At the same time there is a disorientation and 

 displacement of lipid, probably from the general lamellar fabric 

 of the epicuticle, and this results in an increase in the hydration 

 of the lipid and the protein from which the displacement occurs. 

 In this way, the permeability of the cuticle to water and 

 /j-benzoquinone is increased. 



Permeability and Enzyme Activity 



Finally, we can now consider the interesting question of the 

 relation of these changes in membrane permeability to the 

 activity of enzymes which are protected by the environmental 

 influence of the membrane framework. A lipid-free gelatin 

 membrane immersed in a /'-benzoquinone substrate becomes 

 rapidly tanned, but if we now substitute a catechol substrate for 

 the p-benzoquinone, tanning of the membrane does not occur. 

 Wagreich and Nelson ^^ have shown that the enzymic oxidation 

 of catechol results in the production of an intermediary o-quinone. 

 This quinone has tanning properties similar to those of /^-benzo- 

 quinone, and it is readily produced by the action of an enzyme 

 known as peroxidase which can be Extracted from horseradish 

 roots.-^ Catechol is very rapidly oxidized in an aqueous substrate 

 containing peroxidase and hydrogen peroxide, and gelatin 

 membranes in this substrate become rapidly tanned by the 

 diffusible o-quinone. Similarly, we can prepare gelatin mem- 

 branes which contain peroxidase. These also become tanned 

 when in contact with catechol and hydrogen peroxide, but here 

 the reactive o-quinone is formed within the membrane frame- 

 work. Insect cuticle behaves as a membrane of this type, for it 



