D. W. WOOLLEY 



and cyanide have figured prominently in the discovery and differentia- 

 tion of certain enzymic processes. It has seemed probable that, since 

 the inhibitory structural analogues bring about specifically deficiencies 

 of various metabolites with which they act competitively, these 

 analogues might be highly selective inhibitors of an enzyme system 

 involving the structurally related metabolite. This has proved to be 

 so in the case of o-aniinobenzylmethylthiazolium chloride, a structural 

 analogue of thiamin. This compound was an effective inhibitor of 

 the enzyme found in certain marine animals which cleaves the thiazole 

 moiety from the vitamin. Likewise, glucoascorbic acid inhibited the 

 action of ascorbic acid in the oxidation of tyrosine by guinea pig liver. 

 The oxidation of tyrosine by liver was apparently a process which 

 involved ascorbic acid, and in this process glucoascorbic acid and its 

 related metabolite behaved competitively. Furthermore, the action 

 of cozymase, a derivative of nicotinic acid, was inhibited by 3-pyridine- 

 sulfonic acid. This effect of the analogue, however, was not specific, 

 since several other substances of dubious structural relationship to 

 nicotinic acid gave a similar result. The competitive inhibition by 

 malonate of oxidative systems involving the four-carbon dicarboxylic 

 acids was one of the first instances of biochemical antagonism to be 

 explored, and antedated by several years the observations on sulfanil- 

 amide and /?-aminobenzoic acid. Finally, utilization of pantothenic 

 acid by certain bacteria, a reaction which seemed to be enzymic, was 

 inhibited reversibly by thiopanic acid. Here, the antagonist was 

 of value in differentiating the reaction which involved pantothenic 

 acid from glycolysis. Several inhibitors of glycolysis were also in- 

 hibitors of the utilization of pantothenic acid. Thiopanic acid, how- 

 ever, prevented the latter without influencing the former, and thus 

 indicated that the two processes were separable. 



The mechanism of action of various drugs is largely unknown. 

 It may be worth while in our gropings for the desired explanations 

 to consider some biological effects produced by benzimidazole, an 

 agent which causes in animals loss of muscular tone and of ability to 

 respond to stimuli. Also, it prevents the growth of many micro- 

 organisms. Its growth-inhibiting action is reversed competitively by 

 adenine, which, in the form of adenylic acid and of adenosine triphos- 

 phate, is believed to be of considerable importance in muscular con- 

 traction. Because of these facts, it would seem that the pharmaco- 



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