204 PTEROYLGLUTAMIC ACID 



what unsatisfactory by a number of considerations. In the first place, most 

 of the available food analyses for PGA were performed before the existence 

 of CF was recognized so that the values reported represent summations 

 of the growth-stimulating properties of both PGA and CF."^ Moreover, in 

 the case of S. faecalis R assays, there may have been incomplete liberation 

 of PGA and CF from their conjugates. ^'^'^ A disturbing feature of PGA 

 dietary analyses is the apparent great loss of the vitamin after cooking, 

 amounting to approximately 50 to 95 % of the original activity.'^^ PGA 

 determinations on canned foods, except for spinach, were especially low.^^^ 

 These differences between PGA content of fresh raw foods and that of 

 their cooked or canned counterparts have been attributed to a possible 

 binding of the vitamin by the tissues. ^^^ It may be stated, however, that 

 diets deficient in animal protein and green vegetables are low in PGA and 

 CF. It is true, of course, that such diets are also low in vitamin B12 and 

 in amino acids which are concerned in PGA metabolism, so that a number 

 of factors may contribute to the manifest deficiency state. 



Therapeutic responses to the administration of PGA in cases of nutri- 

 tional macrocytic anemia were first reported in 1945^"^ and 1946 ^^''' ^" Of 

 interest is the report of a patient who responded to PGA, relapsed after 

 discontinuing treatment, and subsequently showed a favorable response to 

 pteroylheptaglutamic acid (hexaglutamyl conjugate of PGA). The signifi- 

 cance of this event lies in the reported observations, to be discussed later, 

 indicating that pernicious anemia patients may be unable to utilize effec- 

 tively the naturally occurring hexaglutamyl conjugate and that the meta- 

 bolic defect may be corrected by vitamin B12 administration. It seems 

 probable, although not clearly proved, that the "Wills factor" is identical 

 with PGA including its conjugates. This hemopoietic factor, as supplied by 

 a preparation of autolyzed yeast (Marmite) was shown by Wills and her 

 associates to produce responses in cases of tropical macrocytic anemia which 

 failed to benefit from the prior administration of a purified liver extract 

 (Anahaemin).!^®' ^^ Comparable results were obtained in monkeys. ^^^"^^^ 



1" V. Cheldelin, A. M. Woods, and R. J. Williams, /. Niifrition 26, 477 (1943). 



150 V. Mims, J. R. Totter, and P. L. Day, /. Biol. Chem. 155, 401 (1944). 



1" B. S. Schweigert, A. E. Pollard, and C. A. Elvehjem, Arch. Biochcm. 10, 107 (1946). 



152 M. Ives, A. E. Pollard, C. A. Elvehjem, and F. M. Strong, /. Nutrition 31, 347 



(1946). 

 1" C. F. Vilter, T. D. Spies and M. B. Koch, Southern Med. J. 38, 781 (1945). 

 1" T. D. Spies, /. Am. Med. Assoc. 130, 474 (1946). 



1" G. A. Goldsmith, /. Lah. Clin. Med. 31, 227 (1946); Federation Proc. 5, 232 (1946). 

 i6« L. Wills, Brit. Med. J. I, 1059 (1931). 

 1" L. Wills and P. D. F. Evans, Lancet II, 416 (1938). 

 168 L. Wills and A. Stewart, Brit. J. Exptl. Pathol. 16, 444 (1935). 

 159 L. Wills, P. W. Clutterbuck, and B. D. F. Evans, Biochem. J. 31, 2136 (1937). 

 K!" L. Wills and P. D. F. Evans, Lancet 232, 311 (1937). 



