Folic Acid (Pteroylglutamic Acid) and Related Substances
The development of our present knowledge of folic acid, called pteroylglutamic acid (PGA), resulted from many studies of the nutritional needs of animals, on the one hand, and of bacterial requirements, on the other. It is no wonder that this compound (and closely related molecules) has been assigned a wide variety of designations, since so many test animals and different bacteria have been employed under diverse experimental conditions in the elucidation of its nature. Also, a variety of symptoms were used as deficiency criteria in animals. Further complications surely resulted from the fact that the vitamin occurs in several chemical forms.
A few of the names previously applied to this vitamin include vitamin M (a hematopoietic factor for monkeys), vitamin Be (chick growth factor), factor R (bacterial growth), norite eluate factor (Lactobacillus casei), L. casei factor, vitamin BlO' and vitamin Bu' In 1941 the name folic acid (Latin folium, leaD was assigned to a principle required by Streptococcus lactis R by Mitchell, Snell, and Williams. The term folacin is commonly used now as a synonym for folic acid. In no other instance has the correlation of the work of the bacteriologist and the nutritionist been so important and productive in the success of elucidating our knowledge of a vitamin. An important link between the two fields of investigation was formed in 1941, when investigators at the University of Wisconsin pointed out certain similarities between a bacterial growth factor and a substance required for chick growth.
Activity for L. casei and for the chick and loss of activity on storage for both were shown to be similar in a preparation from liver. Mitchell, Snell, and Williams developed a method for concentrating the vitamin from spinach to 137,000 times the activity of their standard liver preparation. A crystalline product was obtained by several groups of investigators in 1944 from liver, yeast and other natural sources. About this time investigators recognized a difference between fermentation L. casei factor and liver L. casei factor, although the products of chemical degradation were the same.
It developed that the fermentation factor contains three molecules of glutamic acid, one molecule of p-aminobenzoic acid, and a substituted pteridine, while the liver factor is chemically similar save for the fact that only one molecule of glutamic acid is present per molecule of vitamin. In 1946 the isolation, proof of structure, and synthesis of folic acid were described by a group of workers at the Lederle Laboratories.
