D. E. GREEN 



scarcely detectable by the most delicate chemical methods, p-am'ino- 

 benzoic acid can hardly be classified as a typical metabolite. Quite 

 clearly, the term metabolite as applied to /^-aminobenzoic acid must 

 imply merely that it is involved in metabolism. Furthermore, since 

 traces of essential substances are known to participate in metabolism 

 only in the capacity of catalysts, the "essential metabolite" theory boils 

 down to a disguised enzyme theory. In the present state of ignorance, 

 there is some merit in talking of /)-aminobenzoic acid as an essential 

 metabolite until such time as its precise enzymic role is clarified. 

 But when the essential metabolite theory is seriously proposed as an 

 alternative to the enzyme theory, it becomes important to recognize 

 what the concept of essential metabolite really means. As applied to 

 />-aminobenzoic acid, "essential metabolite" is just a term of caution 

 to indicate by implication a catalytic role, without stating it in so many 

 words. But as occasionally happens with terms of caution, their neu- 

 trality defeats their purpose. Essential metabolite has become con- 

 fused by many with metabolite, and its real significance has become 

 lost among those who see only the letter and not the spirit of the term. 



The relation between the sulfonamides and j&-aminobenzoic 

 acid provided a blueprint for designing other chemotherapeutic 

 agents. Every vitamin or prosthetic group theoretically should find 

 its nemesis in some antivitamin. So the hunt began, and not without 

 success. The sulfonic acid analogue of pantothenic acid (pantoyl- 

 taurine) was found to inhibit the growth of some bacteria which re- 

 quired pantothenic acid. The ratio of pantothenic acid to the sulfonic 

 acid analogue determined whether growth or inhibition would take 

 place. Much of the same kind of results were obtained with pyri- 

 thiamin, as antithiamin agent, with pyridine /3-suIfonic acid, as anti- 

 nicotinic acid agent, etc. None of these antivitamins is comparable 

 to the sulfonamides in their efficiency as chemotherapeutic agents; 

 but in these antivitamins, at least, we have the hopeful beginnings of 

 a rational program of chemotherapy. 



From the standpoint of enzymes, chemotherapy would appear 

 to be the science of compounds which go for the enzymic Achilles' 

 heel of an infectious organism without at the same time damaging the 

 host unduly. In other words, the objective is first to find an enzyme • 

 which is present or important in the infectious organism and not in 

 the host, and second to find a drug which specifically inhibits this 



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