I[. niEMISTHY 91 



jireparatioMs wore foiiiul which were effective in the treatment of liuman 

 pernicious anemia hut whicli iiroduced no response in the anemit' monkeys 

 on the experimental chets. These ol>servations thus served to (hstinguish 

 the anti-pernicious anemia factor of h\er from the factor effective against 

 tropical macrocytic anemia. 



Day and coworkers- gave the name "vitamin M" to a factor essential for 

 hematopoiesis in monkeys. This factor was later shown to be pteroylglu- 

 tamic acid by Day el al.,^- who also found that this deficiency disease could 

 be corrected by pteroyltriglutamic acid. Stokstad and Manning^ observed 

 that chicks receiving a diet consisting essentially of washed fish meal, 

 polished rice, riboflavin, thiamine, and a pantothenic acid concentrate 

 responded to an unknown growth factor in yeast, alfalfa, and wheat bran. 

 This factor was designated "factor U" and Avas later shown to be identical 

 with PGA. Hogan and Parrott^ gave the name "vitamin Be" to a factor 

 present in liver which prevented macrocytic anemia in chicks. 



Shortly after the pubhcation of these experiments with animals, Snell 

 and Peterson^ reported that Lactohacillus casei required an unknown growth 

 factor which they termed the "Norit eluate factor." The term "folic acid" 

 was given by Mitchell et al.^ to a substance obtained from spinach, which 

 stimulated the growth of Slreptococcus faecalis R and was active for L. 

 casei. It appeared to have the same microbiological properties as the 

 Norit eluate factor. 



II. Chemistry 



E. L. R. STOKSTAD 



A. ISOLATION 



1. Of Pteroylglutamic Acid (PGA) 



Many papers have appeared describing the concentration and chemical 

 properties of PGA. In the first publication by the Wisconsin workers, Snell 

 and Peterson' reported that this factor was adsorbed bj'^ activated charcoal 

 and Lloyd's reagent, was stable to acid and alkali, could be precipitated by 

 basic lead acetate, and was extracted from aqueous acid solutions by bu- 

 tanol. A later publication by Hutchings et al.- from this same laboratory 

 described additional methods of purification by adsorption on Super Filtrol 

 and formation of a zinc salt. The isolation of a highly active folic acid 



'2 P. L. Day, V. Mims, J. R. Totter, E. L. R. Stokstad. B. L. Hutchings, and x\. H. 

 Sloane, ./. Biol. Chem. 157, 423 (1945). 



> E. E. Snell and W. H. Peterson, ./. BncUrwl. 39, 273 (1940). 

 2 B. L. Hutchings, N. Bohonos, and W. H. Peterson, J. Biol. Chnn. 141, .521 (1941). 



