CATALYSIS AND ENZYMES 305 



shown by experiment ; indeed, acid is commonly used both for hydrolysis and for 

 synthesis of esters and other compounds. Another point, which is illustrated in 

 the example chosen, is that it is not necessary that the two men should be equally 

 excited by the same cause. If the one ran faster than the other, they would meet 

 at a different equilibrium point. What is important to notice is that if they meet 

 anywhere except at either extreme end, they must both have been accelerated. The 

 conclusion to be drawn is that, if any slowly progressing reversible reaction is acted 

 on by a catalyst, and the equilibrium position found to be anywhere except at 

 nearly complete hydrolysis or synthesis, both of these processes must have been 

 accelerated by the catalyst. In theory, therefore, every catalyst is capable of both 

 hydrolytic and synthetic action and, instead of requiring special proof that an 

 enzyme is a synthetic agent, proof must be demanded of any contrary statement. 

 In the case of the ester acted on by lipase, if the hydrolytic reaction alone were 

 accelerated, the synthetic reaction, going on at its own extremely slow pace, would 

 not have proceeded to any perceptible extent before the hydrolytic one was 

 complete. The equilibrium point would inevitably be close to that of complete 

 hydrolysis, instead of being somewhere near one-third of the distance from the 

 synthetic end. 



This point of view is particularly insisted on by van't Hoff (1901, p. 211), and 

 it is interesting to note that, at the time of his death, he was engaged in researches 

 on enzymes with regard to their synthetic action (Cohen, 1912, pp. 575-576). 

 He had already made - important advances in the elucidation of glucoside 

 formation (1910), but, unfortunately, never reached the third part of his 

 programme, the processes in the living organism. There is a pathetic interest 

 attached to these latest researches of the great investigator, in that, as Ostwald 

 says (1912, 1, p. 515), they were paid for with parts of his life itself. A portrait 

 of van't Hoff in 1899 has been given in Fig. 24. 



There are, in practice, many cases where the equilibrium position is so near complete change 

 in one direction that it is held by some workers in this field to show absence of any reverse 

 reaction whatever. Such a case is the action of emulsin on salicin ; even under such conditions 

 of concentration that synthetic action would be most favoured, there appears, to a hasty 

 observer, to be complete hydrolysis. Closer investigation shows, however, that the reaction is 

 not quite complete. Both Visser (1905) and Bourquelot and Bridel (1913) found this incomplete- 

 ness to be the fact and what is of importance is that both sets of independent experiments 

 gave the same equilibrium point. 



This fact obviously means that, even when accelerated by a catalyst, the 

 synthetic reaction is very slow, compared with the hydrolytic one, when emulsin 

 acts on salicin, or its components. The explanation was given by van't Hoft 

 (1910), who pointed out that salicin is the glucoside of a tertiary alcohol, that is, 

 of an alcohol which contains a carbon atom united directly to three other carbon 

 atoms and with its third valency united to hydroxyl (see Bunge Plimmer, 1907, 

 pp. 71-73). The group may be illustrated thus : 



HO CH 3 

 \ 



\CH 3 

 which is tertiary butyl alcohol. 



Now, according to the work of Menschutkin (1879) on esterification, tertiary 

 alcohols are very difficult to esterify, and van't Hoff shows that the same statement 

 applies to the formation of glucosides. A primary alcohol, which contains the 

 group CH 9 OH, on the contrary, is easily esterified or made into a glucoside. The 

 alcohols of our first experiments, iso amyl and ethyl alcohols and glycerol, are all 

 primary, so that the synthetic action is easy and the equilibrium position is a 

 considerable distance from both ends. The synthetic reaction, in those cases 

 where the equilibrium point is close to that of complete hydrolysis, is one that is 

 of inherent chemical difficulty, and the facts given above with respect to the 

 equilibrium position are thus to be accounted for. We shall see later, however, 

 that even a small amount of synthesis is of considerable importance under such 

 conditions that the product is removed as fast as it is formed. 



20 



