316 PRINCIPLES OF GENERAL PHYSIOLOGY 



there is linear proportionality. It is also different where the enzyme concentrations 

 are very far removed from one another, or of high values, being smaller if we 

 compare concentrations of 64, 128, and 256, in arbitrary units, with those of 1, 2, 

 and 4 in the same units. Details of these experiments will be found in a paper by 

 myself (1911, 1, pp. 9094). 



The reader will probably notice at once that these results are precisely what 

 we should expect if the velocity were controlled by adsorption of substrate by 

 enzyme ; it was, in fact, this relationship which first led me to suggest the 

 hypothesis of adsorption as applying to the case (1906, p. 224). 



It is then impossible to formulate a general law, correlating the concentration 

 of enzyme with its activity, and capable of giving numerical results, except one 

 of considerable complexity. Each case must be investigated for itself until we 

 know more of the changes taking place in the colloidal state of the enzyme during 

 the course of the reaction. This state is, no doubt, the cause of the variations 

 of the adsorption exponent which we have met with ; it may have any value 

 between one and two, values above two are rare. 



There are three classes of substances which may next be considered, since 

 they affect the rate at which the enzyme acts. 



1. Electrolytes. Pepsin and trypsin are inactive except in acid or alkaline 

 solutions respectively. Amylase requires neutral salts, which have also a 

 beneficial effect, as a rule, on enzymes generally. The question will be referred 

 to again later. 



2. Co-enzymes. Bertrand (1897) found that the oxidase of Japanese lacquer 

 is ineffective without the presence of manganese and called this substancg the 

 " co-enzyme " of laccase. These oxidation systems will be considered in 

 Chapter XX. 



Magnus (1904) discovered that the lipase of the liver loses its activity when 

 dialysed, but recovers it when bile salts are added. It seems probable that this 

 action is exerted on the enzyme itself, since it applies to the action on soluble 

 esters as well as to that on fats, which might be supposed to be better emulsified 

 by bile salts. These latter, having so great a power of lowering surface tension, 

 are no doubt able to bring about a greater colloidal dispersion of the enzyme, 

 thus increasing its active surface. 



Another interesting case of a co-enzyme is that of alcoholic fermentation. 

 Yeast juice contains an enzyme, or rather enzyme-system, "zymase," which brings 

 about the formation of alcohol and carbon dioxide from sugar. Harden and 

 Young (1906) showed that such juice, filtered through Martin's gelatine filter, 

 which keeps back the colloids, was separated into two constituents, neither of 

 which was active by itself, but became so on mixing again. Since inorganic 

 phosphates increase the activity of yeast juice, it was thought that they might 

 be the co-enzyme, but experiments showed that these alone were incapable of 

 restoring activity to the- colloidal matter left on the filter, and that it was 

 necessary to add boiled yeast juice in addition. Both substances are indeed 

 required. 



3. Anti-enzymes. When a foreign protein is injected subcutaneously into an 

 animal, some kind of a neutralising substance is produced. This is known as the 

 " anti-body," while the injected substance producing it is the " anti-gen." There 

 is as yet no satisfactory proof that any substance other than a protein can act 

 as an antigen. The antibodies are of various kinds, sometimes they precipitate 

 the antigen and are known as precipitins, sometimes they act in neutralising its 

 toxic properties in some other way and are called " anti-toxins," sometimes they 

 cause agglutination of bacteria, " agglutinins," and so on. 



Now statements have been made that when enzymes are used as antigens, 

 anti-enzymes, true antibodies in the above sense, that of Ehrlich, are formed. 

 It is to be noted that a true anti-enzyme must be specific and act only on the 

 particular enzyme which caused its production, its antigen. It is therefore 

 incorrect to describe any substance which retards the action of an enzyme as 

 an anti-enzyme ; otherwise, alkali would have the right to be called " antipepsin." 



The results of certain experiments which I had occasion to make with 



