ANTIBODY AS A SPECIFIC ENZYME INHIBITOR 145 



of immune serum, died from the effects of diphtheria toxin it received. 

 Similar results were obtained with tetanus by Behring and Kitasato. 



In 1891 Ehrlich treated animals with increasing doses of ricin and 

 abrin and found that the toxin was neutralized m vitro when added to 

 the treated animal's serum, proof of neutralization being offered by 

 the fact that when certain proportions of toxin and immune serum 

 were mixed in vitro, these mixtures were innocuous when injected into 

 animals. He proved that the neutralizing action of immune serum 

 upon each of these toxins was specific, that is, the antiserum for abrin 

 did not neutralize ricin, and vice versa. To Ehrlich was also reserved 

 the elucidation of the nature of the acquired immunity to toxins of 

 snakes through the formation of antitoxins in the bodies of the toxin- 

 treated animals, though the immunization against the toxins of snake 

 venom had already been practiced by Sewall (1887), Calmette (1894), 

 and by Eraser (1895). 



These observations led Ehrlich to the conclusion that "the power 

 of toxin to combine with antibodies must depend upon a specific atom- 

 group in the toxin-complex possessing a maximal specific relation to 

 definite atom-groups of the antitoxin complex, so that it rapidly unites 

 therewith, like a lock and key," a figure borrowed from Emil 

 Fischer in describing the action of specific ferments.* 



The observed striking analogy between the specificities of immune 

 and enzyme reactions must have made a deep impression on the minds 



* Pasteur found that Penicillium glaucum decomposed d-tartaric acid and left the 

 1-tartaric acid intact. E. Fischer (1894, 1898) observed that yeast fermented d-hexoses, 

 i.e., glucose, mannose, galactose and fructose, but not the 1-hexoses; a- and ^-methyl- 

 d-glucosides were hydrolyzed by enzymes; in contrast a- and yg-methyl-l-glucosides 

 were not attacked. Whilst a-methyl-d-glucoside was hydrolized by a-glucosidase 

 (maltase) only, /J-methyl-d-glucoside was attacked by emulsin. ^-d-Glucoside was 

 hydrolyzed by /J'd-glucosidase, and /J-d-galactoside by yg-d-galactosidase. This was 

 explained by the fact that glucose and galactose differed stereochemically from each 

 other at the 4-carbon atom. These facts led E. Fischer to believe that there existed 

 a specific enzyme for each substrate. Maltose was believed to be hydrolyzed only by 

 maltase, and in fact, glucoside, disaccharide, trisaccharide and polysaccharide were 

 each believed to be attacked by a specific enzyme. The specific behavior of an enzyme 

 towards the optical antipodes he believed to be conditioned by the optical configura- 

 tion of the enzymes, which was compared with the lock-and-key system; that is, it 

 can function only when it fits the lock. 



Recent observations, however, have shown that a-glucosidase of bottom beer yeast 

 is capable of hydrolyzing a-methylglucoside and maltose (a-glucosido<|4-glucose) 

 (Willstatter, Kuhn and Sobotka, 1924). Likewise saccharase, hydrolyzing saccharose, 

 is capable of hydrolyzing the fructose linkage of raffinose (/j-d-fructose<; >a-glu- 

 cose^a-galactose) (Kuhn, 1923). Emulsin from sweet almond hydrolizes yQ-d-glucoside 

 and its 6-brom-hydrin derivative, ^-d-isorhamnoside, yg-d-xyloside, jg-d-galactoside 



