BIOTIN 



19. ANALOGUES OF BIOTIN 

 Pimelic Acid 



The nutritional requirements of Corynehacterium diphtheriae were 

 studied by J. H. Mueller et al.^ who showed that the growth of this 

 organism was stimulated by various fractions prepared from animal 

 tissues, in addition to a number of amino acids. One of the con- 

 stituents of these fractions was identified as pimelic acid,^ and syn- 

 thetic pimelic acid proved to be equally active. Mueller's observations 

 were confirmed by Evans et al.^ using gravis, intermedius and mitis 

 strains of C. diphtheriae. Du Vigneaud et al.^ showed that biotin 

 could replace pimelic acid for the Allen strain of C. diphtheriae, although 

 pimelic acid produced slightly more growth than biotin at the maximum 

 level of 1-5 /xg. ; biotin was more effective than pim.elic acid, however, 

 at low concentrations. Pimelic acid is probably utilised by some 

 strains of this organism for the synthesis of biotin, much as some 

 strains utilise ^-alanine in place of pantothenic acid. 



Thirteen different organisms tested by W. J. Robbins and R. Ma ^ 

 failed to grow on an otherwise complete mediiun in which biotin was 

 replaced by pimelic acid alone or accompanied by L-cystine, gluta- 

 thione or methionine. 



Isomers of Biotin 



Synthetic ^-biotin and natural biotin had identical growth-pro- 

 moting activities for three bacteria, one yeast and a fungus. /-Biotin 

 and ^/-allobiotin supported the growth of bacteria only in large 

 amounts and this slight activity was probably due to contamination 

 with traces of f^-biotin.^ 



On rats maintained on a diet containing e%g white, ^/-biotin was half 

 as active as natural biotin, '^ whilst /-biotin was without effect at seven 

 and a half times, and f^/-allobiotin at ten times, the level of biotin. 



Synthetic f^-biotin was as effective as natural biotin ^ in promoting 

 growth and preventing dermatitis in chicks fed a purified diet con- 

 taining 15 % of raw eg^ white. /-Biotin and ^/-biotin were inactive. 



Hoxnologues of Biotin 



Rather surprisingly perhaps, increasing or decreasing the length of 

 the valeric acid side-chain of biotin not only almost completely 

 destroys the growth-promoting activity of the molecule but converts 

 it into a growth-inhibitory substance. Although nor-biotin (n = 3) 

 and homo-biotin {n = 5) can replace biotin for Saccharomyces globosus 

 and one strain of S. cerevisiae, they and other homologues are potent 

 antagonists of biotin for other strains of the latter and for S. fragilis, 

 Zygosaccharomyces barkeri and L. helveticus ^^ (page 453). 



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