290 THE BIOCHEMISTRY OF B VITAMINS 



(7) Folic Acid 



The elucidation of the structure and functions of the folic acid group 

 of compounds has come in recent years, so that comparatively little is 

 known as to the relative merits of its various analogues. Folic acid is 

 known to occur in free and bound forms, as the tri- and heptaglutamate, 

 and also in formylated derivatives. Methods for assessing responses gen- 

 erally depend upon hematopoietic response, and a variety of substances 

 have been found to influence such responses (e.g., pyridoxic acids, p. 421). 

 Even 5-methyl uracil (thymine) in doses of 4.5 gm or more produced 

 hematological responses in six patients in relapse stages of Addisonian 

 pernicious anemia, 139 which is in line with the suspected function of folic 

 acid in purine and pyrimidine formation. Indeed, for bacteria at least, the 

 replacement of the pteridin moiety of folic acid by a quinazoline or a 

 benzimidazole ring gives compounds with some biological activity. 140 - 141 

 Petering et al. 14 ' 2 found that a combination of 4-pyridoxic acid and folic 

 acid was better than folic acid alone in stimulating growth and hemo- 

 globin formation in deficient chicks, although other workers have been 

 unable to confirm this. Folic acid and the tri- and heptaglutamate are 

 all active in curing sprue, 143 and are active for monkeys. The mono- 

 and triglutamate at least are active in nutritional macrocytic anemia, 

 and folic acid at least is active in treating pernicious anemia. (The hepta- 

 glutamate has up till now given highly divergent results. 144 * 145 The 

 recently isolated vitamin B ]2 should also be mentioned at this point as 

 a substance which in minute quantities is capable of alleviating pernicious 

 anemia. Both pteroic acid and formylpteroic acid are inactive for L. casei 

 or humans, 140 " 148 while pteroylheptaglutamate is inactive for bacteria, 

 but is twice as active as the monoglutamate for Tetrahymena gelii. 1 * 9 

 Various other possibilities exist for the presence of folic acid activity 

 in natural sources 149a which are more conveniently discussed in a later 

 chapter (pp. 413 to 422). 



(8) Choline 



Because choline is a structural part of such a wide variety of naturally 

 occurring compounds, its analogues in a sense may be considered to be 

 numberless. In the phospholipides, however, when digestive hydrolysis 

 occurs, free choline is doubtless liberated, so that the efficiency of lipide 

 choline is quite high. This variety of choline derivatives, however, makes 

 the assessment of choline requirements difficult, since it involves an esti- 

 mate of the ability of an organism to liberate the choline. 150 In addition 

 to its esters, the various substances involved in choline synthesis are also 

 active in many cases. Mono- and dimethylethanolamine are active in 



