576 NEW AND UNIDENTIFIED GROWTH FACTORS 



bacterial and one protozoal growth systems and one bacterial oxidative 

 system were under study in the four laboratories that independently re- 

 ported the existence of this compound. 



Priority for the discovery of lipoic acid is assigned to Guirard, Snell, 

 and Williams' and to Kidder and Dewey,^ ■ ^ who at an earlier date noted a 

 combined growth effect that was later shown^ to be due to lipoic acid, py- 

 ridoxal, and copper ions. Guirard et al. observed' that the stimulatory effect 

 of acetate upon the growth of Lactobacillus casei could be replaced by small 

 quantities of natural extracts such as liver, yeast, or dried grass juice. They 

 concentrated the active material 44-fold from yeast. The following year, 

 O'Kane and Gunsalus^ found that an unidentified factor from yeast (later 

 called pyruvate oxidation factor®) was necessary in resting cells of Strep- 

 tococcus faecalis, for oxidation of pyruvate, or its anaerobic dismutation to 

 lactate, acetate, and carbon dioxide. Preparations were obtained that were 

 approximately 200 times as potent as the starting material (yeast extract) . 

 Independently of these investigations, Stokstad et al} fractionated the natu- 

 ral supplements described by Kidder and Dewey^ ■ ^ for the nutrition of 

 Tetrahymena geleii and found that the necessary unknowns could be reduced 

 to two. Both of these unknowns produced the same biological response, and 

 it was concluded that they were two forms of the same compound. They 

 named the substance "protogen" because of its effect upon the protozoon. 

 Later,^ these workers found that a strain of Corynehacterium also required 

 protogen for growth. Finally, Kline and Barker^ described what appears 

 to have been lipoic acid as a growth factor for Butyrihacterium rettgeri.^ 

 They concentrated the factor approximately 200-fold from yeast and dem- 

 onstrated the existence of at least three forms. 



The probable identity of protogen, the acetate replacing factor, and the 

 pyruvate oxidation factor was reported by Snell and Broquist,^** who showed 

 a high degree of correlation to exist among the relative potencies of different 

 concentrates for acetate replacement, pyruvate oxidation, and Tetrahymena 

 growth. The compound had been found to be fat-soluble, and because of 

 this and its adsorption characteristics it was also thought to be similar to 



1 B. M. Guirard, E. E. Snell, and R. J. Williams, Arch. Biochem. 9, 381 (1946). 



2 V. C. Dewey, Biol. Bull. 87, 107 (19-14). 



3 G. W. Kidder and V. C. Dewey, Arch. Biochem. 8, 293 (1945). 



^ E. L. R. Stokstad, C. E. Hoffmann, M. A. Regan, D. Fordham, and T. H. Jukes, 



Arch. Biochem. 20, 75 (1949). 

 5 D. J. O'Kane and I. C. Gunsalus, J. Bacterial. 54, 20 (1947). 

 •5 D. J. O'Kane and I. C. Gunsalus, J. Bacteriol. 56, 499 (1948). 

 ^ E. L. R. Stokstad, C. E. Hoffmann, and M. Belt, Proc. Sac. Exptl. Biol. Med. 74, 



571 (1950). 



8 L. Kline and H. A. Barker, /. Bacteriol. 60, 349 (1950). 



9 I. C. Gunsalus, L. Struglia, and D. J. O'Kane, J. Biol. Chem. 194, 859 (1952). 

 i» E. E. Snell and H. P. Broquist, Arch. Biochem. 23, 326 (1949). 



