314 PRINCIPLES OF GENERAL PHYSIOLOGY 



to the intervention of electrical charge. The slight diminution in hydrogen ion 

 concentration caused by the addition of blood serum is sufficient to bring about 

 great retardation in the action of emulsin (Bayliss, 1912, 2). Trypsiri is inactive 

 except in slightly alkaline reaction, and there is a particular narrow concentration 

 of hydrogen ion in which it, as indeed enzymes in general, are most active. Now 

 it has been shown by Brailsford Robertson and Schmidt (1908-9) that, during 

 the course of a digestion by trypsin, there is a progressive increase of hydrogen 

 ion concentration, or diminution of hydroxyl ion, due to the production of 

 amino-acids, which, combining with the free alkali originally added, diminish the 

 alkalinity, and thus retard the action of the enzyme more and more as the reaction 

 goes on. It is found, indeed, that the addition of amino-acids has a powerful 

 effect in slowing trypsin digestion. 



An observation that has probably been made by many workers with trypsin is that, 

 supposing that one starts a digestion of caseinogen with trypsin, adding only the optimal 

 amount of alkali, after a week or two in the incubator one finds that the digest is distinctly 

 acid to litmus, and the rate of action can then be made in increase by addition of more alkali. 



A reaction, then, can be caused to proceed more rapidly by removal of the 

 products, as was pointed out by Kronecker (1874), and this result is due, not only 

 to reversibility, but also to the fact that the products are more or less toxic to 

 the enzyme itself. 



As would be expected, the sensibility of enzymes to various substances is much great IT 

 than that met with in ordinary chemical reactions. It is held by some investigators that there 

 is a special "affinity" of each enzyme for certain products of its action, in that the rate of 

 change is affected more by these than by other related substances. Thus, E. F. Armstrong 

 (1904, 2) found that fructose retards the action of invertase more than the corresponding 

 concentration of glucose does, and the statement is made that invertase is "controlled" 

 by fructose. The fact, however, that fructose also " controls " the action of maltase more 

 than glucose does (Philoche, 1908, p. 243), although it is not a constituent of the system 

 concerned, suggests that the relationship is not one of a chemical nature between the 

 constitution of the enzyme and of its substrate. The excessive sensibility of enzymes to 

 acidity and to some inorganic salts warns us that great caution must be exercised in the 

 interpretation of results of this kind. Bourquelot (1913, 2, p. 3) finds that the hydrolysis of 

 arbutin is retarded by hydroquinone, but not that of salicin. Hence the action is not on the 

 enzyme itself, and increase of the reverse reaction is suggested. 



The acceleration of rate, in the course of the action of invertase, is probably 

 due to the production of some substance in small amount which increases the 

 activity of the enzyme. Acid does this, and it has been stated that an acid is 

 produced in small quantities during the action of inveitase, and it may perhaps 

 be Isevulinic acid. So far as I am aware, no measurements of the hydrogen ion 

 concentration during the reaction have been made. 



There is a certain similarity between this production by an enzyme of 

 substances which affect its own activity and the process called by Ostwald 

 " Autocatalysis " (1902, II. (2), pp. 263-266). In the first illustration at the 

 beginning of the present chapter we saw that the spontaneous hydrolysis of 

 methyl acetate in water is greatly accelerated by the addition of acid. Now 

 in the hydrolysis itself, free acetic acid is formed, which must act as a catalyst, 

 although not a powerful one. Moreover, it increases in amount by its own 

 activity, so that, if we determine the velocity constant at different times, we 

 find that it increases at a greater and greater rate. 



In an experiment of this kind which I performed, at the beginning of the reaction the 

 velocity constant was 49 x 10~ 7 , in nineteen days it had risen to 593 x 10~ 7 , and in forty-two 

 days to l,498xlO~ 7 . In half-normal hydrochloric acid, it was initially 1,600 tinii's that in 

 water and equilibrium was reached in about six hours, so that, if there were no autocatalysis 

 in water the attainment of equilibrium would have taken 6x 1,600 hours, or 400 days. This 

 fact may assist the reader to realise how slow the spontaneous reaction is, and how ini|>ossililr 

 it is for the equilibrium position to be unaltered by acid unless the catalyst accelerated both 

 the hydrolytic and synthetic reactions. 



Perhaps a few more details will be useful with regard to the phenomenon 

 of autocatalysis. When the curve of a reaction of this kind is plotted with 

 time as abscissae and actual rate of change as ordinates, it is found to have 

 an S shape. The rate is slow at first, becomes quicker and then slows again. 

 This course is typical of autocatalysis and is, obviously, due to the deficiency 



