Folic Acid

 Folic Acid

PKGhatak, MD

Folic acid is a water soluble yellow crystalline substance. It is a chemical made of Pteridine, p-aminobenate and Glutamic acid. Glutamic acid may be present as monoglutamate but usually exists in polyglutamine forms, containing anywhere from 2 to 7 glutamic acid residues. About 30 different derivatives of folic acid are present in nature. In the plasma, the Folic Acid (FA) is pteroylmonoglutamic acid, but within the cells, folic acid exists in polyglutamic form. In the blood, the majority of folic acid is present in RBC. The normal Plasma FA level in adults is 3 to 17 ng/ml. RBC folate level resembles body storage and deficiency appears 90 days before low plasma FA.

Other names.

Citrovorum factor. An essential growth factor for bacteria Leuconostoc citrovorum was detected and named citrovorum factor and later was identified to be folic acid but the name remains. At one time FA was called vitamin B9.

Folic acid however cannot enter the cells as such, until it is reduced to Tetrahydrofolate (THF) by the enzyme THF Reductase, B12 methyl coenzyme and NADH acting as H donors. Once inside the cells, lysosomal enzymes convert it into polyglutamate and then combine with substrates to form Folic acid coenzymes.

Folic acid coenzymes are single C-atom transfer and utilization agents. One [C-atom] maybe 1. Formyl group [-CHO], 2. Formate [- H COOH] , 3. Hydroxymethyl [– CH2.OH]. These three groups are metabolically interchangeable. THF coenzymes combine with one of the above one atom C and form and play a very important role in DNA, RNA and phospholipids synthesis.

Dietary source.

Source - fruits, leafy vegetables, field mushrooms, liver, and fortified food items.

Daily requirement is 400 micrograms for adults and for pregnant women 600 mcg/day. A FA dose of 5000 mcg/day to pregnant women is harmful to the developing child, and increased incidence in respiratory allergy, insulin resistance and delayed psychomotor development are seen in these children.

The Folic acid storage in the liver is good for 3 months of use and the total amount is 5 mg.

Absorption of FA.

Polyglutamic FA in food is converted to monoglutamate in the intestinal mucosa, then FA is absorbed in the upper small intestinal epithelial brushed border by a transported protein. Renal tubular cells reabsorb FA from glomerular filtrate.

Transport of FA in and out of cells requires conversion of FA to polyglutamate and monoglutamate and vice versa. And each phase requires a specific transporter protein.

Actions of FA coenzymes are necessary for methylation. Folic acid is required in the formation of choline, Serine, Glycine, Methionine. and histidine.

Purine and thymine are used in DNA synthesis.

FA coenzymes convert amino acid histidine to glutamic acid through an intermediate step where foraminmonoglutamic acid is formed. This is the basis of the Figlu test to detect folic acid deficiency. This test is just of historical importance, the blood FA test has replaced Figlu test.

The function of FA.

It is an essential vitamin for all cells of the body for cell growth, maturation, and repair. FA is utilized for DNA, RNA, mRNA and phospholipid synthesis. It is necessary for the methylation of fatty acids, metabolism of several amino acids. Growth and development of the fetus. 

FA deficiency.

Deficiency. Alcoholism, dietary habits, overcooked vegetables in a large volume of water.

Drug interference- anticonvulsants, oral contraceptives, Methotrexate. Trimethoprim-sulfamethoxazole and Sulfadiazine. Aminopterin (MTX) is a permanent folic acid antagonist and is used in the treatment of Leukemia and immunosuppressant, used as an adjunct in order to reduce steroid dose.

The medical condition leading to deficiency - pregnancy, hemolytic anemia, exfoliative dermatitis, GI mucosal atrophy, psoriasis.

Effects of FA deficiency.

The tissues which turn over rapidly exhibit the earliest changes in the development of the nucleus but the cytoplasm continues to develop normally. Blood cells- RBC, WBC and Platelets are not only decreased in number but also deformed. Since RBCs have no nucleus, the nuclear abnormality is clearly visible in peripheral WBC. CBC. Anemia. Most RBCs are large and come in various thicknesses and sizes giving an increase in RWD, PVC, and a low HCT. Leukopenia and polysegmented neutrophils and decreased Platelet count. Erythroblasts in peripheral blood. 

Neurological.

Changes are noted in a fetus and newborn, commonly spina bifida and anencephaly.

Folic acid deficiency is common in pregnancy due to increased demand by the fetus which cannot be met by diet alone. WHO recommends fortification of rice, cereals, flour, pasta and bread with folic acid. It plays a vital role in the synthesis of the nucleus of all cells.

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