THE FOLIC ACID COMPLEX 



of potential rather than actual folic acid in a substance was a measure 

 ot its vitamin M activity. They also seemed to suggest that xanthop- 

 terine might be a precursor of vitamin M, although Wright et al.^^ 

 offered another suggestion, namely, that free folic acid in rat liver 

 was converted by liver enzymes into a substance having little or no 

 microbiological activity and that the reaction was inhibited by 

 xanthopterine. Although, on the basis of their experimental data, 

 they could not exclude the possibility that folic acid might be syn- 

 thesised from xanthopterine, they favoured the hypothesis of a 

 metabolite-antimetabolite relationship. 



That vitamin M is simply free plus combined folic acid appears 

 to be a valid conclusion from the most recent paper on vitamin 

 M deficiency, in which Day et al.^^ reported that intramuscular injec- 

 tion of a highly purified L. casei factor, which was relatively inert 

 towards 5. faecalis R, cured both the anaemia and leucopenia of 

 vitamin M-deficient monkeys in a total dose of 3 mg. given over 

 several days ; prompt remission of the blood dyscrasia and a dramatic 

 improvement in the clinical condition of the animals occurred. Xantho- 

 pterine was only slightly active when given orally, and was inactive 

 by injection, again suggesting that it might serve as a precursor of 

 vitamin M. The L. casei factor became as active as a standard 

 vitamin Be preparation in stimulating S. faecalis R after treatment 

 with vitamin Bo conjugase (page 479). 



Anti-sulphonamide Factor 



Totter and Day's unconfirmed observation on the effect of xantho- 

 pterine on sulphasuxidine-treated rats, although misleading at the 

 time, served a useful purpose in directing attention to the close 

 analogy between the effects of vitamin M deficiency in monkeys and 

 sulphonamide administration in rats. Thus, although the response of 

 sulphasuxidine-treated rats to xanthopterine was suspect, the response 

 to folic acid was definite, and both G. J. Martin ^^ and C. A. Elvehjem 

 and his colleagues ^^ found that folic acid plus biotin cured the symp- 

 toms caused by administration of sulphasuxidine to rats. 



Pantothenic acid, inositol and _/)-aminobenzoic acid have at 

 various times been claimed to cure the achromotrichia (greying of 

 hair) and alopecia (loss of hair) resulting from the administration 

 of sulphonamides, but the response to the combined effect of folic 

 acid and biotin was more striking than any obtained with the other 

 vitamins. 



The results obtained by Martin and by Elvehjem and his colleagues 

 were confirmed by F. S. Daft and W. H. Sebrell,*^ who found that 

 crystalline folic acid cured the leucopenia and granulocytopenia caused 



462 



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