FATS AS ESSENTIAL DIETARY COMPONENTS 889 



stimulating growth of L. casei and of other lactic acid bacilli. Trager-" 

 considered that this growth factor was related to oleic acid, and that both 

 were related to the utihzation and function of biotin. However, he found 

 that the properties of the material did not correspond to those of oleic 

 acid or of any previously described vitamer of biotin. Although Trager-^^ 

 was of the opinion that this ether-soluble substance was a component of 

 the non-saponifiable residue, Hofmann and Axelrod-^^ were unable to 

 confirm this hypothesis. The latter workers reported that the substance 

 with biotin-like activity in beef and human plasma occurred exclusively 

 in the saponifiable portion of the lipid. When the fraction was esterified 

 with diazomethane, the resulting methyl esters obtained by distillation 

 possessed high biologic activity. On a weight basis, oleic acid was shown 

 to have about the same potency as the plasma distillate. It was also 

 found^^^ that the Hquid acid fraction of the plasma which contains oleic, 

 linoleic, and arachidonic acids had a greater growth activity for the Lacto- 

 bacillus than did the original fraction, although the unsaturated acids 

 were also found to have some synergistic action. ^^^ A number of sugges- 

 tions have been offered as to the reason why biotin and the unsaturated 

 fatty acids can replace each other in promoting bacterial growth. Trager-'*" 

 studied the growth of yellow fever mosquito larvae (Aedes aegypti) in 

 biotin-free media, and found that larval growth was very slow, and that 

 metamorphosis did not occur. However, relatively low concentrations of 

 oleic acid, lecithin, and related compounds supported growth commensurate 

 with that obtained with low concentrations of biotin. He concluded 

 that biotin functions in the synthesis of fatty compounds or of substances 

 containing fatty acids, such as lecithin. Rubin and Scheiner-*^ demon- 

 strated that biotin is primarily concerned with the synthesis of oleic acid. 

 Thus, biotin antagonists such as homobiotin, trishomobiotin, homobiotin 

 sulfone and trishomobiotin sulfone have no depressing effect upon the 

 growth of Lactobacillus casei on a biotin-free medium, provided oleic acid 

 is used as a biotin substitute. Moreover, Williams and Fieger^^- reported 

 that avidin sufficient to combine with 1,000 m^u of biotin did not prevent 

 the lipid stimulation of L. casei in the absence of biotin. These facts would 

 seem to indicate that oleic acid is not active by virtue of effecting a syn- 



2" W. Trager, Proc. Soc. Exptl. Biol. Med., 64, 129-134 (1947). 



238 K. Hofmann and A. E. Axelrod, Arch. Biochem., 14, 482-483 (1947). 



239 A. E. Axelrod, M. Mitz, and K. Hofmann, /. Biol. Chem., 175, 265-274 (1948). 

 2« W. Trager, /. Biol. Chem., 176, 1211-1223 (1948). 



2" S. H. Rubin and J. Scheiner, Arch. Biochem., 23, 400-410 (1949). 

 2« V. R. Williams and E. A. Fieger. J. Biol. Chem.. 170 399-411 (1947). 



