VITAMIN B9

VITAMIN B9

A. History Day, for the first time, showed the existence of this nutritional factor by demonstrating that yeast extract could cure cytopenia, a disease experimentally induced in monkeys. The potent factor was obtained from spinach leaf and this led to its nomenclature as folic acid, FA (foliumL = leaf). The official name of this vitamin is folacin. This is also known as liver Lactobacillus casei factor as it was isolated from liver and was shown as necessary for the growth of lactic acid bacteria. Hogan called this as vitamin Bc. However, a number of other compounds or factors , having similar or different biochemical functions but closely related to folic acid, were isolated from different sources. These are fermentation Lactobacillus casei factor, Streptococcus lactis R (SLR) factor, Bc conjugate and citrivorum factor, CF.

B. Occurrence: Folic acid and its derivatives (tri- and hepta-glutamyl peptides) are widely distributed in biological world. A few important sources are liver, kidney, tuna fish, salmon, yeast, wheat, dates and spinach. Root vegetables, sweet potatoes, rice, corn, tomatoes, bananas, pork and lamb contain little folid acid.

With improper cooking, folacin contents are destroyed, like thiamine.

C. Structure: A molecule of folic acid consists of 3 units : glutamic acid, p-aminobenzoic acid and a derivative of the heterocyclic fused-ring compound pterin. Its molecular formula is C19H19O6N7.
The various vitamins of B9 group differ from each other in the number of glutamic acid groups present ; the additional glutamic acid group being conjugated in peptide linkages. For example, folic acid contains one, fermentation Lactobacillus casei factor three and Bc conjugate seven glutamic acid groups. The conjugates (i.e., compounds having more than one glutamic acid groups in the molecule) are ineffective for some species as these species do not possess the enzyme conjugase which is necessary for the release of free vitamin. Citrivorum factor, however, differs from other vitamins of B9 group in the structure of one of the rings of the pterin moiety.
D. Properties: Folic acid is a yellow crystalline substance, slightly soluble in water but insoluble in fat solvents. It is stable to heat in alkaline or neutral solutions only. It is inactivated by sunlight.

E. Metabolism: The reduction products of folic acid act as coenzymes. An enzyme, folic reductase, reduces folic acid to dihydrofolic acid (DHFA or FH2), the latter compound is further reduced by dihydrofolic reductase to 5,6,7,8-tetrahydrofolic acid (THFA or FH4). The formation of FH4 from FA is associated with the oxidation of NADPH or NADH and requires the presence of ascorbic acid.
The vitamins of B9 group are involved in one-carbon metabolism in a way similar to the twocarbon metabolism in which CoA is involved. THFA acts as an acceptor of a one-carbon unit either from formate (in which case 5,6,7,8-tetrahydrofolic acid is formed) or from formaldehyde (in which case 5-hydroxymethyl-5,6,7,8-tetrahydrofolic acid is formed). THFA is also involved in the transfer of the methyl group and in the utilization of single carbons (formate) in the synthesis of serine, methionine, thymine, purines, choline and inosinic acid.
Folic acid, in conjunction with ascorbic acid, also appears to be related to tyrosine metabolism.

Citrivorum factor (CF) is 5 formyl derivative of tetrahydrofolic acid and is so named because it supports the growth of Leuconostoc citrivorum. CF is about one thousand times more potent biologically than folic acid. Its chemical name is folinic acid. During the conversion of FA to CF, vitamin B12 and ascorbic acid are also required. Citrivorum factor ( and also folic acid to a lesser degree) are concerned in the production of an agent that stimulates the formation of normal RBCs. It is interesting to note that the bacteria, which require PABA for growth, also utilize FA with almost equal ease. Recent studies have shown that folic acid provides protection against Alzheimer’s disease. Folic acid is, however, essential for lactation in rats and hatchability of eggs in chicks, turkeys and guinea pigs. Rats, dogs and probably man do not need folic acid because the intestinal bacteria synthesize sufficient quantity of this vitamin.

F. Deficiency: In chicks, a lack of this factor leads to anemia. Rats develop achromotrichia (failure in normal pigmentation of the hair). The monkeys show macrocytic anemia (anemia characterized by the presence of giant RBCs), leukopenia, diarrhea and edema (retention of water by skin tissues).

On a worldwide basis, deficiency of folic acid is believed to be the most common form of vitamin undernutrition. In man, the folic acid deficiency leads to megaloblastic anemia, glossitis and gastrointestinal disorders. Pregnant women and infants are also particularly vulnerable. Folic acid deficiency is a major feature of tropical sprue, in which there is a general deficiency in absorption of many nutrients from the small intestine.
Folic acid has been successfully used in the treatment of certain macrocytic anemias such as those developed in sprue and anemias of pellagra, pregnancy and infancy. However, the long-held hope that it would cure pernicious anemia (caused by avitaminosis B12) has not been held true since it fails to cure the neurological lesions of the disease.
G. Human requirements: The daily dietary allowance of folic acid is 0.1 mg for infants, 0.2 mg for children and 0.4 mg for adult men and women. Pregnant mothers may, however, requireup to 0.8 mg per day.