VIII. EFFECTS OF DEFICIENCY 39 



ill the rat and also demonstrated a favorable effect of PABA on the mor- 

 tality rate of the newborn. 



The etiology of aehromotriehia in the rat appeared to be further com- 

 plicated when Martin^' • **- reported that black rats receiving a purified 

 sulfaguanidine-containing diet adeciuate in calcium pantothenate and 

 PAB.V become gray. The graying could be cured with folic acid concen- 

 trates. Similar findings were reported by Wright and Welch^'* with black 

 rats recei\'ing succinylsulfathiazole. Accompanying the aehromotriehia seen 

 in the latter studies were low hepatic stores of pantothenic acid. The aehro- 

 motriehia responded fa\-orably, and the hepatic stores of pantothenic acid 

 were restored to normal with the daily oral administration of folic acid and 

 biotin. It was concluded that fohc acid and biotin are concerned with "utili- 

 zation of pantothenic acid in the rat." 



Some clarification with respect to the role of PABA in nutrition resulted 

 when it was announced by Angier and coworkers^'* that PABA is a structural 

 moiety of folic acid. There seems little doubt but that the beneficial effect 

 observed from the feeding of PABA, as, for example, in the studies of 

 Briggs and coworkers,^^ may be directly attributable to an increased syn- 

 thesis of fohc acid on the part of intestinal microorganisms (and possibly 

 even tissue cells^®) in the presence of the structural component PABA. 



A plausible explanation for the occurrence of aehromotriehia in rats 

 receiving diets containing both pantothenic acid and PABA, and its cure 

 with folic acid and biotin, is possible as a result of three con^•erging lines 

 of investigation. Firstly, it has been demonstrated by Lipmann and co- 

 workers^^ that pantothenic acid is present in tissues largely, if not en- 

 tirely, in the form of coenzyme A, a ''modified" nucleotide containing ade- 

 nine as the purine component. Secondly, free pantothenic acid has been 

 found by Wright et al.^^ to have a high renal clearance so that pantothenic 

 acid probably does not remain long in the animal body without some mecha- 

 nism for retention b^^ tissue cells. Thirdly, PABA in the form of fohc acid, 



«' G. J. Martin, Proc. Soc. Exptl. Biol. Med. 51, 353 (1942). 



82 G. J. Martin, Federation Proc. 1, 58 (1942). 



" L. D. Wright and A. D. Welch, Science 97, 426 (1943). 



8^ R. B. Angier, J. H. Boothe, B. L. H\itchings, J. H. Mowat, J. Semb, E. L. R. 



Stokstad, Y. SubbaRow, C. W. Waller, D. B. Cosulich, M. J. Fahrenbach, M. E. 



Hultquist, E. Kuh, E. H. Northey, D. R. Seoger, J. P. Sickels, and J. M. Smith, 



Jr., Science 103, 667 (1946). 



85 G. M. Briggs, .Jr., T. I). Luckey, R. C. .Mills. C. .\. Elvehjom, and V.. B. Hart, 

 Proc. Soc. Exptl. Biol Med. 52, 7 (1943). 



86 F. S. Daft, Public Health Repts. (U.S.) 62, 1785 (1947). 



87 F. Lipmann, N. O. Kaplan, G. D. Novelli, L. C. Tuttle, and B. M. Guirard, ./. 

 Biol. Chem. 186, 235 (1950). 



88 L. D. Wright, K. H Beyer, H. R. Skeggs, H. F. Russo, and E. A. Patch, Am. J. 

 Physiol. 145, 633 (1946). 



