566 BIOTIN 



present in the total volume of the medium. This finding speaks in favor of 

 biotin synthesis in the presence of oleic acid.^®^ 



Many lactic acid bacteria require both biotin and oleic acid for optimal 

 growth. '^^' 1^3-18^ 



It was claimed^®^ that the intramuscular injection of a fat-soluble frac- 

 tion (FSF) — a neutral oil — obtained from hydrolyzed plasma into chicks 

 fed a diet high in egg white reduced the severity of their dermatitis. The 

 similar injection of oleic acid did not have such an effect, nor could the 

 effect be produced by the oral administration of the material from plasma. 

 Through countercurrent distribution and by chromatographic adsorption, 

 fractions were prepared which showed as high a specific activity ior Lacto- 

 bacillus casei as oleic acid but which differed from oleic acid in physical 

 properties. ^^® The chemical nature of the active substance has not been 

 determined. Since on prolonged heating with alkali the activity of this 

 fat-soluble fraction from plasma goes into the saponifiable fraction and 

 behaves toward Lactobacillus casei as oleic acid,^" it is highly probable 

 that oleic acid represents its specific active principle, perhaps in a less 

 toxic form than free oleic acid. 



c. Inhibitory Analogs 



Several analogs of biotin may have an inhibitory effect, usually on a com- 

 petitive basis, on the utilization of biotin or other biotin compounds by 

 various organisms. The inhibitory activities of a compound are given in 

 terms of the molar inhibition ratio, ^°^ which has been defined as the number 

 of molecules of the inhibitor necessary to prevent the biological effect of 

 one molecule of biotin. The molar inhibition ratio^"^ of a given inhibitor 

 to biotin is obtained experimentally by determining the amount of the 

 inhibitor required to reduce the growth obtained with 0.0002 y of biotin 

 to the level of growth obtained with 0.0001 y of biotin. The inhibition index 

 just necessary for complete inhibition of growth is usually greater than 

 that obtained for half -maximum inhibition of growth. 



d. Desthiobiotin and Related Compounds 



Desthiobiotin stimulates the growth of Saccharomyces ccrevisiae in a 

 biotin-free medium. On the other hand it will competitively interfere with 

 the utilization of biotin by Lactobacillus casei^^^- ^" (p. 562). Several other 

 analogs of desthiobiotin were prepared and tested for their inhibitory 



"2 E. A. Andrews and V. R. Williams, J. Biol. Chem. 193, 11 (1951). 



i«3 B. L. Hutcliings and E. Boggiano, J, Biol. Chem. 169, 229 (1947). 



'«" A. R. Whitehill, J. J. Oleson, and Y. SubbaRow, Arch. Biochem. 15, 31 (1947). 



»«6 B. M. Guirard, E. E. Snell, and R. J. Williams, Arch. Biochem. 9, 361 (1946). 



los W. Trager, Proc. Soc. Expll. Biol. Med. 64, 129 (1947). 



1" K. Hofmann and A. E. Axelrod, Arch. Biochem. 14, 482 (1947). 



