ANALOGS OF OTHER VITAMINS 589 



before the biotin, but not afterward (Axelrod et al., 1948). This could mean 

 that these analogs cannot displace biotin once it is bound or that they in- 

 hibit in some way the formation of an active form of biotin. Biotin is inac- 

 tivated by kidney slices, possibly by removal of fragments from the side 

 chain, by biotin oxidase, and this enzyme is inhibited by several analogs 

 competitively (see accompanying tabulation) (Baxter and Quastel, 1953). 

 There is thus the possibility that some analogs can conserve biotin in the 

 tissues as well as inhibit its svnthesis or function. 



4 1 Concentration , . , , , , . . 



Analog (Analog)/ (biotin) % Inhibition 



{raM ) 



Analogs of cyanocobalamin (vitamin B^g) have not been extensively stud- 

 ied because of the complexity of the structure. 5,6-Dimethylbenzimidazole 

 is a component of cyanocobalamin and l,2-dimethyl-4,5-diaminobenzene is 

 a precursor in the synthesis. Analogs of these substances are often inhibi- 

 tory to bacterial growth and the biosynthesis of vitamin B^g. 1,2-Dichloro- 

 4,5-diaminobenzene inhibits the synthesis of vitamin B^g in bacteria and the 



HaC^^^^^^X^ ^ Clv^/^^^NHa 



,iU, 



H,C^ ^^^ ^N^ Cr ^^ ^NHa 



5, 6-Dimethylbenzimi- 1, 2-Dichloro-4, 5- 



dazole diaminobenzene 



growth of those bacteria requiring vitamin B^g (WooUey and Pringle, 1951). 

 Vitamin B^g is unable to counteract these inhibitions. Although 5,6-dimeth- 

 ylbenzimidazole can be used by the rat to form vitamin B^g, this sub- 

 stance is inhibitory to Lactobacillus lactis, and like a number of analogs, is 

 able to inhibit the synthesis of vitamin B^g in these bacteria (Hendlin and 

 Soars, 1951). These inhibitions do not appear to be competitive with vi- 



