172 PTEROYLGLUTAMIC ACID 



liver extracts. Ransone and Elvehjem^ later showed that "fohc acid con- 

 centrates" prepared from liver were effective in increasing growth on the 

 sulfonamide diet. 



The activity of pure PGA in correcting the blood dyscrasia was reported 

 by Daft and SebrelP and Wright and Welch. ^ The blood of normal rats 

 contains 10,000 to 15,000 total leucocytes and 2000 to 4000 granulocytes. 

 These counts were reduced, respectively, to 700 to 2000 leucocytes and 10 

 to 500 granulocytes after 30 to 90 days feeding on a diet containing sulfa- 

 guanidine. The daily feeding of 10 7 of PGA or 20 7 of pteroyltriglutamic 

 acid for 4 days increased the leucocytes and the granulocytes to normal. 

 In some cases there was a surge of leucocytes and especially the granulocytes 

 to higher than the normal levels. 



Definite evidence that PGA is actually synthesized in the intestinal tract 

 comes from the observation that the depressed growth resulting from sul- 

 fonamide feeding can be restored by the feeding of rat feces as well as yeast 

 and yeast extract (Light et al.^). 



A thorough investigation of the effects of sulfonamide feeding to rats has 

 been made by Daft, Sebrell, and coworkers at the National Institutes of 

 Health, and their work has been excellently reviewed in a Harvey Lecture.'' 

 One of these symptoms which has been frequently observed in rats receiving 

 sulfonamides is hypoprothrombinemia. This accounts for the subcutaneous 

 hemorrhages observed on these types of diets.'' This hypoprothrombinemia 

 can be prevented or cured by the feeding of vitamin K, folic acid concen- 

 trates,* and 7?-aminobenzoic acid.^ The effect of p-aminobenzoic acid can 

 be readily accounted for by its ability to reverse the bacteriostatic effect 

 of the sulfonamide in the intestine and thus permit resumption of bacterial 

 synthesis of vitamin K. The effect of the fohc acid concentrates cannot be 

 as readily accounted for. Their method used in preparation of the folic 

 acid concentrate precludes the presence of a fat-soluble form of vitamin K. 

 Unfortunately, the effect of pteroylglutamic acid on hypoprothrombinemia 

 under conditions employed by Welch and Wright* has not yet been re- 

 ported. 



Rats receiving a sulfonamide have an increased susceptibility to anemia 

 induced by frequent bleeding. ^° Administration of pteroylglutamic acid has 



3 B. Ransone and C. A. Elvehjem, J. Biol. Chem. 151, 109 (1943). 



* F. S. Daft and W. H. Sebrell, Public Health Repts. (U. S.) 58, 1542 (1943). 



6 L. D. Wright and A. D. Welch, Science 98, 179 (1943). 



6 R. F. Light, L. J. Cracas, C. T. Olcott, and C. N. Frey, ./. Nutrilion 24, 427 (1942). 



^ W. H. Sebrell, Harvey Lectures Ser. 39, 288 (1943-44). 



8 A. D. Welch and L. D. Wright, /. Nutrition 25, 555 (1943). 



3 S. Black, R. S. Overman, C. A. Elvehjem, and K. P. Link, ./. Biol, (licui. 145, 137 



(1942). 

 "> A. Kornberg, H. Tabor, and W. IT. Sebrell, Aw. J. Phi/.^iol. 142, 604 (1944). 



