248 VITAMINS 



The glutamic acid derivative of rhizopterin, formylpteroylglutamic acid, 

 or formyl folic acid, has been prepared synthetically and found to possess 

 the typical vitamin activity of other members of this group. It probably 

 also occurs naturally. Rhizopterin itself, however, does not relieve the 

 symptoms of folic acid deficiency in higher animals. 



Very recently a substance needed for normal growth of the bacterium 

 Leuconostoc citrovorum (the so-called "citrovorum factor") has been 

 found to be closely related to formylpteroylglutamic acid, from which 

 it can be obtained by reducing and heating. The product, named folinic 

 acid by one group of investigators and leucovorin by another, has been 

 shown (Consulich, et al, Pohland, et al.) to have the following formula: 



.^ 



H 

 N^ /N. H H 



HsN-C^ C" XH2 C — C COOH 



.L. 



// \ 



^ '^ H(i-CH,HN-C C-CONHCHCHaCH^COOH 



I I C=C 



OH CHO ^ ^ 



Folinic acid (or leucovorin) 



In many tests folinic acid possesses higher activity than other members 

 of the folic acid group. It may be the metabolically active (coenzyme) 

 form of this vitamin, or at least it may be more closely related to the 

 coenzyme than pteroylglutamic acid itself. 



Physiological function 



This vitamin is essential for a wide variety of living organisms, and, 

 in fact, is probably needed by all living cells. The outstanding deficiency 

 symptoms in higher forms (mammals, birds) are anemia, leucopenia (a 

 reduced number of white blood cells) , weight loss, oral lesions, and diar- 

 rhea. In the chick the deficiency also results in abnormally poor 

 feathering. 



That several hurhan diseases are the result of a lack of pteroylglutamic 

 acid or related substances is indicated by the improvement which follows 

 their administration. The best example is sprue, a disease characterized 

 by macrocytic anemia (enlarged red blood cells), leucopenia, glossitis 

 (inflammation of the tongue) , diarrhea with large amounts of fatty ma- 

 terial in the feces, weight loss, and poor absorption of food from the intes- 

 tine. Daily doses of 10 mg. of pteroylglutamic acid or of the triglutamate, 

 teropterin, result in prompt relief of these symptoms. Related conditions 

 described as nutritional macrocytic anemia and macrocytic anemia of 

 pregnancy are similarly benefited. Pernicious anemia patients are bene- 

 fited somewhat, but the improvement is temporary and incomplete, in 

 contrast to the effects of vitamin B12 (see below). 



