326 PRINCIPLES OF GENERAL PHYSIOLOGY 



cases, where the enzyme is not uniformly distributed, rate of diffusion must play 

 a part in the first stage of the particular heterogeneous reaction, as, in fact, is found 

 by experiment, since shaking such systems accelerates the rate of change. When 

 the enzyme is in colloidal solution, although it forms a separate phase, it is com- 

 paratively uniformly distributed, so that the diffusion distances are very small and 

 we can, with caution, apply the formulae of velocity of reactions developed for 

 homogeneous systems. Adsorption of substrate on the surface of the enzyme phase 

 is the next stage, as we saw in describing heterogeneous reactions in general. This 

 probably takes place with great rapidity as soon as the components are sufficiently 

 near together. Chemical reaction follows ; but, under conditions in which it takes 

 place slowly, cold for example, it is possible to separate the actual adsorption 

 compound of enzyme and substrate. The " compound " of starch and amylase has 

 been prepared by Starkenstein (1910) and by Philoohe (1908, p. 393), that of 

 fibrin and pepsin by von Wittich (1872, p. 444), those of trypsin with starch, 

 caseinogen, and charcoal, and of amylase with caseinogen by myself (1911, 1). It 

 will be noted that it is not necessary that the substrate should be one on which 

 the enzyme acts in order that adsorption may take place. 



A further point of interest is that electrolytes behave in this process in the same way as 

 that in which they behave in what we have called above "electrical adsorption" (page 58), 

 as shown by myself in the case of trypsin (1911, 1). If the enzyme and the substrate are 

 both negatively charged, a certain obstacle to adsorption exists, since, if it took place, it 

 would increase the electrical energy of the surface. If a bivalent ion, say Ca' ', is present, 

 the charge on the surface is reversed and adsorption facilitated. In this way the favourable 

 action of electrolytes in many cases can be explained. 



Whether the formation of an intermediate compound of a chemical nature 

 between the enzyme and adsorbed substrate takes place as the next stage is, as yet, 

 uncertain. It has not been shown to occur, so that the precise nature of what 

 happens after adsorption still remains in the dark. 



The work of Wohler, Pliiddemann, and Wohler (1908) is of some importance 

 in this connection. Their investigations concern the catalytic action of various 

 oxides and of platinum on the oxidation of SO in the manufacture of sulphuric 

 acid. They show that any sulphites or oxides of the ordinary kind are inadmis- 

 sible as intermediate chemical compounds between catalyst and substrate. If such 

 a compound is to be assumed, it must be an endothermic one, such as a peroxide. 

 They regard their experiments as more favourable to the theory of acceleration by 

 increased concentration due to adsorption, but do not consider them as definitely 

 deciding the question. 



The possibility of increased chemical potential brought about by molecular 

 forces in the act of concentration on the surface, as pointed out by Hardy, must 

 not be forgotten. 



A difficulty should be mentioned here. We suppose that the natural state of 

 equilibrium is brought about rapidly by increased concentration on the surfaces of 

 enzymes. But, as Prof. Hopkins reminds me, supposing that the different 'com- 

 ponents taking part in the reaction are not equally adsorbed, the position of 

 equilibrium would not be the same on the enzyme as in the body of the solution. 

 It will be clear, however, that the conditions controlling adsorption are so complex 

 that no statements can be made with regard to the case of enzymes until actual 

 experiments have been made with pure preparations. 



The following illustration may assist the reader in understanding the facts of heterogeneous 

 reactions. I must apologise for its apparently trivial nature. Imagine a number of snails in 

 the neighbourhood of a strawberry. As soon as a snail, in the course of its wanderings, 

 becomes sensible of the presence of the food, it proceeds towards it. This is the preliminary 

 diffusion, and would perhaps be more like the real kinetic process if we suppose that the snail 

 was insensible of the existence of the strawberry until it accidentally came into contact with 

 it. The next stage, that of adsorption, follows rapidly as the animal attaches itself to the fruit. 

 If nothing more happens, there is no chemical reaction. The final, chemical stage is the 

 devouring of the food and its subsequent hj'drolysis. It is obvious that the rate of this final 

 stage is proportional to the number of snails "adsorbed." It will also be noted that it is not 

 in linear ratio to the number at work. The more there are, the more they interfere with one 

 another, and, when the strawberry is completely covered, the advent of more snails will not 

 further increase the rate of disappearance, since the newcomers cannot get at the fruit. The 

 strawberry here corresponds to the enzyme ; we may imagine that, instead of the fruit, we 



