METABOLITE ANTAGONISTS 233 



Pyrithiamine causes a thiamine deficiency disease in mice, which may 

 be cured or prevented by the administration of sufficient thiamine (Wool- 

 ley and White, 1943). Neopyrithiamine is reported to be four times as 

 active as pyrithiamine for the rat (Wilson and Harris, 1949). 



Biotin antagonists. Many biotin vitamers are known which are highly 

 specific. The efficiency of an antibiotin in some instances may depend 

 upon whether biotin or one of its vitamers is the competing metabolite. 

 The formulas of two of the compounds are given below. Compare with 

 the formulas of biotin and desthiobiotin given in Chap. 9. 



CO CO 



/ \ / \ 



HN NH HN NH 



CHs— CH Cn(CH.2)5— SO3H H2C CH(CH2)5— COOH 



Sulfonic-acid analogue of desthiobiotin Imidazolidonecaproic acid 



Desthiobiotin and imidazolidonecaproic acid differ only by a methyl 

 group. Desthiobiotin was found to act as a biotin vitamer for Saccha, 

 romyces cerevisiae and other yeasts (Dittmer et al., 1944; Lilly andLeonian- 

 1944), while imidazolidonecaproic acid is an antibiotin for S. cerevisiae 

 (Dittmer and Du Vigneaud, 1944). Both compounds are antibiotins 

 for Lactobacillus casei. The sulfonic-acid analogue of desthiobiotin was 

 shown by Duschinsky and Rubin (1948) to be more active against desthio- 

 biotin and oxybiotin than against biotin for S. cerevisiae. The replace- 

 ment of a carboxyl group by a sulfonic-acid group appears to be a rather 

 general method of changing a metabolite into an antagonist. Further 

 examples of this will be cited in connection with pantothenic and amino- 

 acid antagonists. 



Egg white contains a specific protein which combines with biotin and 

 thus renders this vitamin inactive. This inactivity is due to the molecu- 

 lar size of the avidin-biotin complex, which prevents its absorption by 

 organisms. Raw egg white may be used to produce experimental biotin 

 deficiency in animals. Avidin is no longer active after heating, and 

 bound biotin is released by this treatment. This specific protein has 

 been used to separate biotin vitamers into two groups, for avidin com- 

 bines only with those compounds w^hich have an intact urea ring structure. 

 The papers of Eakin et al. (1941) and Burk and Winzler (1943) may be 

 consulted for further details. 



Pantothenic acid antagonists. Yeasts are the only fungi which have 

 been reported to be deficient for pantothenic acid, and in most instances 

 /3-alanine replaces the intact vitamin molecule. One of the commonly 

 studied pantothenic acid antagonists is the compound called pantoyl- 

 taurine. The formulas for pantothenic acid and pantoyltaurine are 

 given belo'rt 



