INTRODUCTION 



isolated by C. Schopf and E. Becker ^8 from the wings of the brimstone 

 butterfly (Gonepteryx rhamni) and, in 1941, R. W. Simmons and 

 E. R. Norris ^^ showed that both synthetic xanthopterine and xanthop- 

 terine isolated from liver could cure an anaemia observed in Chinook 

 salmon. J. R. Totter and P. L. Day,^^ therefore, tested xanthopterine 

 in anaemic monkeys and found that, whilst it relieved the blood 

 changes in nutritional cytopenia, it failed to cure the other mani- 

 festations of vitamin M deficiency. They also claimed that xan- 

 thopterine cured the leucopenia and increased the growth rate of 

 sulphas uxidine-treated rats, but this claim was not substantiated 

 by the work of B. Ransone and C. A. Elvehjem ^^ or of Day et al.^^ 



Although xanthopterine had a definite beneficial effect on vitamin 

 M-deficient monkeys, the effect of folic acid was even more striking,^^ 

 the growth rate being increased and the leucopenia and granulocyto- 

 penia relieved. The loss of hair (alopecia) was not, however, remedied 

 by folic acid, whereas biotin cured this condition but did not affect 

 the blood picture. Pantothenic acid, choline, _/)-aminobenzoic acid, 

 pyridoxine and inositol were without appreciable effect in vitamin M 

 deficiency, but a highly purified sample of the L. casei factor relieved 

 the granulocytopenia in this condition.^* Folic acid also cured fish 

 anaemia,^^ although it had only one-fifth the activity of xanthopterine. 

 On the other hand, xanthopterine failed to cure anaemic vitamin 

 Bc-deficient chicks. ^^ 



These data suggested that vitamin M was closely related to folic 

 acid, vitamin Be and the L. casei factors and possibly identical with 

 one of them, whereas xanthopterine was a simpler type of substance 

 altogether and an inadequate substitute for these factors in the 

 treatment of vitamin M-deficient monkeys. 



An objection to the hypothesis that folic acid might be identical 

 with vitamin M was that the folic acid contents of various substances, 

 as determined by the original microbiological method of assay using 

 L. helveticus and S. faecalis R, completely failed to account for the 

 vitamin M activities of the same substances when tested on monkeys. 

 Totter et al.,^'^ following up an observation of L. D. Wright and A. D. 

 Welch ^^ that fresh rat liver could synthesise folic acid from xanthop- 

 terine, incubated a preparation of brewers' yeast with fresh rat liver, 

 fresh chicken liver and liver from a vitamin M-deficient monkey. On 

 assaying the digests with S. faecalis R, they obtained a 15-fold or 

 even larger increase in the folic acid content. 



When synthetic xanthopterine was incubated with the liver pre- 

 parations in the same way, considerable amounts of folic acid were 

 found to have been produced, except in the case of chicken liver. 

 These results appeared to indicate that yeast contained a precursor, 

 which liver tissue could convert into folic acid, and that the amount 



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