GREEN : PHYtilOlJJGICAL FUNCTION, ENZ YME C HEM 1ST R Y 5^7 



toxic agent discovered in Chemical Warfare Research, has been shown 

 to inhibit the enzyme systems involved in the metaboHsm of acetic 

 acid. The classical pharmacological reagents, strychnine, eserine, and 

 prostigmine, have been shown to exert their effects exclusively by virtue 

 of their paralysis of cholinesterase. The effects of cyanide on cyto- 

 chrome oxidase, fluoride on enolase, and chlorine on the triosephos- 

 phoric dehydrogenase, are other examples of this correlation. Perhaps 

 even more unexpected, has been the identification of various toxins with 

 enzymes. Thus, spreading factor, the agent which facilitates the 

 rapid diffusion of injected substances through dermal tissue, has been 

 shown to be identical with hyaluronidase, a mucolytic splitting enzyme. 

 The hemolytic principle of Clostridium welchii toxin and that of snake 

 venom have been shown to be lecithinases, and the hemolytic effects 

 are completely explicable in terms of their ability to weaken the lipoid 

 membrane of the red blood cell by hydrolysis of the lecithin contained 

 therein. During the war, some English workers, led by McFarlane,* 

 identified one of the toxins produced by the gas gangrene organism as 

 collagenase, a proteolytic enzyme which dissolves the connective tissue 

 sheath of muscle. The action of this enzyme explains the pulping of 

 muscle observable in advanced cases of gas gangrene poisoning. At 

 the present moment, it would be premature to assume that all specific 

 pharmacological agents which work at high dilutions are active by 

 virtue of their effects on enzyme systems. On the other hand, it is 

 pertinent to point out that no other principle of mechanism has been 

 established for any pharmacological agent which has been studied. 

 Apart from the dictates of caution, there is no good reason not to 

 anticipate that, eventually, all effects of specific pharmacological agents 

 will be reducible to terms of enzyme chemistry. 



The study of endocrines has always been one of the most active fields 

 of physiological investigation, and it is of interest to inquire to what 

 extent hormones can be related to enzyme phenomena. Until quite 

 recently, hormones were held up as notable exceptions to the rule that 

 substances which act at high dilutions must be enzymes or parts of 

 enzymes, or must specifically affect some enzyme system. Some recent 

 research, however, fails to confirm the hormones as exceptions to the 

 enzyme-trace substance thesis. No doubt, everyone is aware of the 

 epoch-making discovery of Cori and his group,^ that one of the hor- 

 mones of the anterior pituitary inhibits the action of hexokinase, and 

 that, in turn, this inhibition is released by insulin. We have here 

 a clear blueprint for the way in which hormone antagonism can be 

 effected. A key enzyme system which controls some metabolic process 



