626 THE BIOCHEMISTRY OF B VITAMINS 



Organisms which do not require pantothenic acid in their nutrition are 

 usually not affected by pantoyltaurine. This phenomenon is widespread 

 among the analogues of pantothenic acid and will be discussed separately. 

 The toxicity of pantoyltaurine for Streptobacterium plant arum was pre- 

 vented to some extent by large concentrations of /^-alanine, and to a 

 larger extent by mixtures of pantolactone and /3-alanine. Since the mix- 

 tures of pantolactone and /^-alanine do not promote growth in the ab- 

 sence of pantothenic acid, it appears that either a chemical or enzymatic 

 conversion of the pantoyl radical of the analogue to pantothenic acid 

 takes place during the testing. 



Early reports 48 indicated that pantothenic acid deficiency in mice 

 could be produced by long-continued oral administration of pantoyl- 

 taurine, but this has not been substantiated. On the contrary, no toxic 

 symptoms have been observed on the administration, either orally or 

 subcutaneously, of pantoyltaurine to mice 49 ~ 51 or rats. 51 



Insulin-treated, depancreatized dogs on a diet deficient in pantothenic 

 acid were fed 1 g of pantoyltaurine daily. After three days, complete 

 refusal of food occurred, but during the first three days with constant 

 food intake, the urinary nitrogen rose, whereas hemoglobin and cell vol- 

 ume fell sharply. 52 It has not been indicated whether pantothenic acid 

 has a beneficial effect in preventing these effects. 



Pantoyltaurine, however, constitutes the first case of an effective 

 chemotherapeutic agent being designed in accordance with the concept 

 of competitive analogue-metabolite growth inhibition. Mcllwain and 

 Hawking 51 reported that rats were protected from 10,000 lethal doses of 

 a virulent strain of streptococcus and less completely from 1,000,000 

 lethal doses by frequent subcutaneous doses of pantoyltaurine. Although 

 pantoyltaurine is rapidly excreted by rats, the ratio of pantoyltaurine to 

 pantothenic acid in the blood could be maintained above the range neces- 

 sary for in vitro inhibition. Administration of pantothenic acid with a 

 subsequent increase in its concentration in the blood resulted in reversal 

 of the therapeutic effect of pantoyltaurine, indicating that the mode of 

 action in vivo was analogous to that in vitro. Because of a higher con- 

 centration of pantothenic acid in the blood of mice, pantoyltaurine did 

 not exert such a protective action for these animals. Sulfonamide-resist- 

 ant streptococci were just as sensitive to pantoyltaurine as the nonresist- 

 ant strains. 



In a series of studies on the mode of action of pantoyltaurine, Mc- 

 llwain 53 found that low concentrations of pantoyltaurine inhibited the 

 initiation of growth of ^-hemolytic streptococci, but, when the analogue 

 was added to growing cultures, the inhibitory effect on growth was not 

 apparent until after a latent period of an hour or more. The action of 



