516 ANNALS NEW YORK ACADEMY OF SCIENCES 



I want to make, however, is that these abnormalities which cover the en- 

 tire gamut of physiological dysfunction can be explained completely in 

 terms of certain enzyme systems. Vitamin Bi, B2, Bg, and the P-P 

 factor have all been shown to be the prosthetic groups of certain 

 enzyme systems. When these vitamins are not available in the diet, 

 the active enzymes cannot be formed in the cell. In consequence of 

 the failure of these enzyme systems to function properly, an abnormal 

 physiological situation develops, which, if uncorrected, will lead to 

 death. Which organ first registers the effect of a particular deficiency 

 is determined by the amount of the reserves of enzymes containing the 

 vitamin and by the relative importance of this set of enzymes in the 

 economy of the organ. Thus, in Bi deficiency in the pigeon, the brain 

 is the first organ to register disturbed function, presumably because 

 there are no reserves of this vitamin in the brain and because the 

 active enzyme formed by the vitamin plays a key role in the metab- 

 olism of brain. One may well raise the point that, if, as in the avita- 

 minosis, the causal link between the physiological disturbance and the 

 effect on enzyme systems is unquestioned, then surely there is a good 

 case for assuming the same link between the normal physiology and 

 enzyme systems. 



Woolley^ has introduced the use of anti-vitamin reagents which, by 

 virtue of their structural resemblance to the vitamins, are able to pre- 

 vent the vitamins either from being incorporated into enzymes or 

 from functioning as prosthetic groups. These anti-vitamins produce, 

 in a relatively short period, the same syndromes which arise from de- 

 priving the diet of an animal of a particular vitamin. Not only are 

 these anti-vitamins valuable for speeding up the process of avita- 

 minosis, but the profound pharmacological effects which they induce 

 permit correlations between the action of reagents on certain enzyme 

 systems and the pharmacological consequences. In other words, the 

 anti-vitamins have focussed attention on the fact that the effects of 

 certain, if not all, pharmacological agents can be explained completely 

 in terms of effects on enzyme systems.^' ^ In recent years, a rich litera- 

 ture has grown up to deal with this correlation. There are now at least 

 14 instances in which the pharmacological effects of certain reagents can 

 be explained in terms of a specific effect on an enzyme system. Thus, 

 iodoacetic acid, which induces muscle rigor, has been found to inhibit, 

 in minute concentration, the triosephosphoric dehydrogenase which 

 catalyzes an essential step in lactic acid formation. This paralysis of 

 the triosephosphoric dehydrogenase accounts for all the pharmacolog- 

 ical effects produced by iodoacetic acid. Fluoroacetic acid, the highly 



