50 ENZYMES 



it approaches the character of a protein, possibly a glycoprotein, with increasing 

 proteolytic activity.^ Analyses of enzymes purified as completely as possible 

 do not have great worth, for the "purified" enzymes are probably far from pure; 

 however, it is of some importance that the.y vary greatly in the proportions of 

 carbon, hydrogen, and nitrogen which they contain, indicating that possibly dif- 

 ferent enzymes may be of very different nature. The enzjanes have been found 

 to possess definite electrical charges; in neutr-il solutions trypsin is negative or 

 amphoteric, pepsin and invertase negative (Michaelis).^ Macallum has shown 

 microchemically that phosphorus is closely associated with the formation of 

 zymogen granules in cells, which seem to be started in the nucleus; and there are 

 many other observations suggesting that certain ferments are closely related to 

 the nucleo-proteins. This is particularly true of the oxidases, which seem also 

 to contain iron and inanganese. A final point of importance in support of the 

 protein nature of enzymes is that pepsin destroj^s trypsin and diastase, while 

 trypsin destroys pepsin.' 



So uncertain, however, is our information concerning the chemical nature of 

 the enzymes, that it has become possible for an hypothesis to be developed urg- 

 ing that enzymes are immaterial, that the actions we consider as characterizing 

 enzymes are the result of physical forces which may reside in many substances, 

 and perhaps even free from visible matter, but the weight of evidence at present 

 available is entirely in favor of the view that enzymes are specific colloidal sub- 

 stances, although perhaps of widely differing chemical nature. A valuable piece 

 of evidence of the material existence of enzymes is their specific nature, lipase 

 affecting only fats, and trypsin only proteins, indicating chemical individuality. 

 They are true secretions, formed within the cell by recognizable steps; and, 

 furthermore, when injected into the body of an animal, they give rise to the forma- 

 tion of specific immune bodies that antagonize their action. Emil Fischer's 

 work with the sugar-splitting enzymes, moreover, indicates that they owe their 

 action to their stereochemical configuration. He prepared two sets of sugar de- 

 rivatives which differed from each other solely in the arrangement of their atoms 

 in space (i. e., isomers) and found that one specific enzyme would split members of 

 only one of the varieties, while another enzyme would act only on the variety 

 with the opposite isomeric form. These experiments make it very probable that 

 there must be a certain relation of geometrical structiu-e between an enzyme and 

 the substances it acts upon, and leaves little question of its material nature. 



Bredig has found that colloidal solutions of metals have many of the properties 

 of true enzymes, accomplishing many of the decompositions produced by en- 

 zymes, being affected by temperatures of nearly the same degree, and even being 

 "poisoned" by substances that destroy or check enzj^mes.^ The only possible 

 explanation of these observations seems to be that the enzyme effects are brought 

 about by surface -phenomena. A colloidal solution of platinum, as far as is known, 

 differs from a piece of metallic platinum solely in the enormously great amount of 

 surface it offers in proportion to its weight, and it is well known that surfaces may 

 affect chemical action. Hence we have the possibility that some enzyme actions, 

 at least, may depend upon the existence of a very large surface, and since by no 

 means all colloids are enzymes, that this surface must bear a certain relation in 

 form to the surface of the body that is to be acted upon. 



The Principles of Enzyme Action 



The effects produced by enzymes, which at one time were con- 

 sidered quite unique and remarkable, have no\v been made compara- 

 tively plain, chiefly through the observations of Ostwald on related 



5 Bokorny (Biochem. Zeit., 1919 (94), G9) finds -that the amount of formalde- 

 hyde fixed by emulsin supports the hypothesis that this enzyme is a protein. 



" Bioclieni. Zeit., 1909 (l(j), 81 and 480; (17), 231. 



' Falk lias ol)tained evidence that ester-splitting enzymes may be proteins 

 owing their activity to the presence in the molecule of active groupings, perhaps 

 of enol-lactim structure, — C(OII) = N — . B.y treating pure proteins with alkali, 

 which favors the fornuition of enol-lactim groupings, the proteins were made to 

 acquire esterase properties. (See Science, 1918 (47), 423.) 



" See also Fischer and Hooker, J. Lab. Clin. Mini., 1918 (3), 373. 



