COENZYMES DERIVED FROM B VITAMINS 173 



results have been interpreted as showing that a biotin coenzyme is 

 destroyed by subjecting the cells to an acid environment; that the 

 coenzyme can be resynthesized from adenylic acid and biotin by fresh 

 preparations, but that on standing the enzymes bringing about the 

 synthesis of the coenzymes deteriorate; and that yeast extract contains 

 the intact coenzyme and, hence, can reactivate the older preparations. 



The Role of Biotin in the Synthesis of Oleic Acid. Oleic acid and 

 related lipides, in the presence of aspartic acid, can effectively replace 

 biotin in the medium of certain lactobacilli that would otherwise require 

 this vitamin 179 > 18 °- 181, 182, 1S3 and can satisfy the biotin requirement of 

 mosquito larvae. 184 This fatty acid can also effectively reverse biotin 

 inhibitors. The results of such investigations indicate that biotin functions 

 in the biosynthesis of oleic acid. Efforts to prove that the reverse is true, 

 i.e., that oleic acid is a precursor of biotin (presumably the aliphatic side 

 chain attached to the biotin nucleus) , have not been successful. 179 Equally 

 unsuccessful have been the attempts to ascribe the activity of the acid 

 solely to some physical action (such as alteration of cell permeability) . 

 The function of biotin in the synthesis of oleic acid is not one in which 

 carbon dioxide is fixed, for no carbon dioxide (isotopically labelled) is 

 taken up when biotin is used to satisfy the oleic acid requirement. 164 



Biotin Coenzymes. The question concerning the number of biotin 

 coenzymes cannot be satisfactorily answered until the number of "biotins" 

 is known. There seems to be irrefutable evidence for the existence of two 

 chemically distinct isomers (Section D), cc-biotin and /?-biotin, having 

 identical biological properties in all systems in which they have been 

 compared. There is still some question concerning the exact structure of 

 the a-isomer, but on the basis of the configuration proposed it is difficult 

 to see how the two structures could exist in equilibrium or be readily 

 interconverted. 



In addition to these two isomers a number of uncharacterized sub- 

 stances of diverse complexities have been shown to possess varying degrees 

 of biotin activity. The existence of these biotin isotels * has been estab- 

 lished by comparing the biotin activities of naturally occurring substances 

 with respect to their ability to stimulate growth in different organisms, 185 

 their avidin combinability, 185 their rate of migration during chromato- 

 graphic separations, 186 and their effectiveness in counteracting the growth 

 inhibitions produced by biotin analogues. 186 If the composition and dis- 

 tribution of the biotin coenzyme (s) resembles that of other B vitamin 

 coenzymes, then it can be assumed that one or more of these naturally 



* Chemically distinct compounds which perform the same physiological function. 

 Williams, R. J., Science, 98, 386 (1943). 



