292 SCIENCE PROGRESS 



really exists. Both of the possibilities mentioned are capable 

 of experimental test. 



On the whole, then, we may take it that when proper account 

 is taken of the reversible nature of enzyme action and of the 

 action of some of the products of the reaction on the activity 

 of the enzyme itself (positive or negative auto-catalysis), the 

 unimolecular logarithmic formula, deduced from the law of mass 

 action, satisfactorily applies to the phenomena in question. 



When we proceed to investigate the rate of change more in 

 detail, we find that this simple law does not apply to the initial 

 and final stages of the reaction — at all events, in the cases which 

 have been investigated up to the present time. (I refer to those 

 of lactase and maltase as investigated by Frankland Armstrong, 

 and of trypsin as investigated by myself.) Although the greater 

 part of the reaction follows the logarithmic law, with the 

 qualifications above referred to, the initial stage and the final 

 stage follow a linear course. In other words, it is found that 

 equal amounts of the substrate are hydrolysed in equal times, 

 notwithstanding the change in its concentration which is taking 

 place. As Frankland Armstrong explains this result, it is due 

 to the combination which takes place between the enzyme and 

 the substrate as a necessary preliminary to the hydrolysis 

 of the latter. As to the nature of this combination and the 

 evidence for its existence, more will be said later ; for the 

 present we may assume that some kind of intimate association 

 does take place. When, therefore, at the commencement of the 

 reaction, the concentration of the substrate is considerably in 

 excess of that of the enzyme, practically the whole of the latter 

 is in combination with substrate ; and since it will not be set free 

 to attack a further quantity of substrate until the first is hydro- 

 lysed, it is obvious that as long as the substrate is in considerable 

 excess equal amounts of it will be split in equal times. As the 

 concentration of the substrate diminishes, the amount at any 

 time in active association with enzyme will be proportional to 

 this concentration, so that the rate of change will follow the law 

 of mass action. In the final stage the amount of change is again 

 equal in equal times, due now to the enzyme being in excess, so 

 that it is able to attack the whole of the substrate available. 



Moore has pointed out that, by taking into consideration 

 the reversibility of the reaction and also the alteration of the 

 intensity of the action of the enzyme, due to some effect of 



