June 22, 1916] 



NATURE 



353 



between enzyme and substrate, but their existence has 

 not been demonstrated, and what I may venture to 

 call Faraday's view has the advantage of simplicity, 

 and thus the support of WiHiam of Occam's "razor." 



The important question of the synthetic action of 

 enzymes demands a little attention at this point. All 

 reactions may be regarded as being, in principle, 

 reversible or balanced, and the greater part of those 

 of the living organism are found experimentally to be 

 so. If we take for consideration those enzymes the 

 action of which consists in the addition or removal of 

 the elements of water, we find that, as would be 

 expected from the law of mass action, the position of 

 equilibrium in the presence of a large excess of water 

 is \'er}- near to that of complete hydrolysis, and this 

 is the state of affairs in the usual laboratory experi- 

 ments. On the other hand, the less water is pre- 

 sent, the greater is the preponderance of the opposite — 

 synthetic — aspect. Take the classical case of ethyl 

 acetate. If the ester and water are mixed in mole- 

 cular proportions, hydrolysis to acid and alcohol occurs 

 until two-thirds of the ester are decomposed. More- 

 over, the same final composition is obtained if we 

 commence with acid and alcohol, and so work in the 

 other direction. But these reactions proceed by them- 

 selves with extreme slowness, taking months before 

 coming to an end. But the presence of a catalyst, 

 such as mineral acid, brings about equilibrium in an 

 hour or so, and we notice that it is the same as the 

 spontaneous one. An enzyme, known as lipase, also 

 brings about equilibrium rapidly. The important point 

 in respect of the mechanism of living cells is that by 

 changing the available amount of water, the reaction 

 may be made to proceed in either direction at will. 

 The series of curves given by Armstrong and Gosney 

 (Proc. Roy Soc, 88B, p. 176) show this fact very 

 clearly. Further, if the equilibrium is brought about 

 rapidly, even if to any position except thafof com- 

 plete change in one or the other direction, the enzyme 

 must accelerate hoih reactions, and any hypothesis of 

 special "" synthesising " enzymes is superfluous. This 

 is essentially the position taken by van't Hoff in the 

 work with which he was engaged at the time of his 

 death. What is required, then, is a means by which 

 the cell is enabled to change the available water at 

 the disposal of reactions occurring therein. We do 

 not as yet know the precise nature of such mechanisms, 

 but there is reason to believe that they are provided 

 by changes in the surface area of colloidal consti- 

 tuents or in the power of imbibition possessed by 

 certain contents of the cell. 



We here come across an interesting problem which 

 cannot be said to be solved satisfactorily at present. 

 We have seen that the equilibrium position of an 

 ester system when reached rapidly under the action 

 of a soluble catalyst is the same as the spontaneous 

 one. But there is a certain difference when a hetero- 

 geneous catalyst, or enzyme, is used. Nevertheless, 

 the equilibrium is a true one, being in the same posi- 

 tion when approached from either end. The amount 

 of butyric acid combined as amyl ester in a particular 

 system under acid catalysis was found by Dietz to 

 be 88 per cent, of the total ; under the action of the 

 enzyme lipase it was only 75 per cent. This fact has 

 given rise to various suggestions, and has troubled 

 people's minds because it appears to give a possibility 

 of evading the second law of energetics. Now, it was 

 pointed out to me by Prof. Hopkins that, on the hypo- 

 thesis of a rapid attainment of equilibrium by con- 

 densation on the surface of the enzyme, it Is necessary, 

 if the natural equilibrium is to be unaltered, that ad- 

 sorption of all the components of the system should be 

 the same proportion of each, because the position of 

 equilibrium must be the same on the surface of the 

 enzyme as that which results in the body of the solu- 

 NO. 24.34. VOL. 97] 



tion. In the presence of a large excess of water, it 

 does not seem likely that a dirterence of equilibrium 

 owing to this cause could be detected. But this should 

 be possible when the equilibrium position is nearer 

 the middle, so to speak, and I am at present engaged 

 in exf>eriments on the question. At any rate, ditter^ 

 ence in adsorption may be the cause of the pheno- 

 menon of Dietz. It would simply imply that w-ater is 

 adsorbed by the enzyme in relatively larger proportion 

 than the other constituents of the system. It should 

 be remembered that the solvent in these experiments 

 was amyl alcohol containing about 8 per cent, of water, 

 and, as Arrhenius has shown, all substances present 

 are adsorbed, although the laws governing the relative 

 proportion of these various substances are not yet 

 completely worked out. 



We see, by consideration of the facts relating to the 

 action of enzymes, how important a part is played by 

 changes in the rate of reactions, and there are two 

 further points to which attention has been directed by 

 Prof. Hopkins. Take, first, a series of reversible 

 reactions in which the products of one form the start- 

 ing point of the next following : — 



^-Z^'S^-ZIZQ-ZZDZH etc. 



If the rate at which B is converted into C is greater 

 than that at which A changes into B, it is obvious 

 that the amount of B present at any moment may be 

 extremely small, although the whole of the final pro- 

 ducts have passed through the stage. The fact warns 

 us from estimating the importance of any particular 

 constituent of the cell by the quantity to be obtained. 



The second point is this. Suppose that there are 

 two independent reversible reactions, both leading to 

 the same product, C. 



and that A — >C is more rapid or easier than B — >-C. 

 This latter reaction will be practically absent, being 

 balanced by the excess of C. But, if the former 

 reaction is abolished by removal of A, then B — >-C 

 will take place in proportion as C is used up in other 

 reactions. Thus, uncier special conditions, a reaction 

 may take place which is not detectable under normal 

 conditions, although capable of taking place. 



One of the most difficult questions is the manner In 

 which the various components of the cell are prevented 

 from entering into chemical reaction except when 

 required. Enzymes, for example, are not always in 

 activity. The conception which states that the cell 

 consists of numerous minute "reaction chambers,'* 

 separated from one another by membranes, seems to 

 present most possibilities. These membranes must be 

 regarded as capable of removal and of reconstruction, 

 or reversible as regards their permeability. The food 

 vacuoles of an Amoeba may serve as an illustration 

 of such chambers on a comparatively large scale. In 

 these vacuoles digestion processes are going on inde- 

 pendently of other reactions in various parts of the 

 same cell protoplasm, although this latter behaves 

 as a liquid. 



The general conclusion to which we arrive is that 

 velocity oj reaction plays an exceedingly important 

 part in the regulation of cell mechanics. I venture to 

 think that the conception is destined to replace static 

 points of view, such as that of " lock and key " or 

 the fitting together of molecular groupings. That 

 there is still verv much to be discovered is obvious. 

 We have to find out how the living cell is able to 

 modify and adjust together the large number of 

 reactions known to the chemist. The study of the 

 methods by which the rate of these reactions is 

 affected is one of the most valuable o* those accessible 

 to us. 



