Folic acid

Question 1

Structure of folic acid

Answer 1

Folic acid consists of three components, pteridine ring, p-amino benzoic acid (PABA) and L-glutamic acid. In a folic acid molecule, the number of glutamic acid residues varies from one to seven. Folic acid usually has one glutamic acid residue.

Question 2

Active Form of Folic Acid

Answer 2

Tetrahydrofolate (THF) is the active form of folic acid. Folate is enzymatically reduced in a two-stage process in tissues to yield the dihydro and then tetrahydrofolate, which requires vitamin C.

Question 3

Sources of folic acid

Answer 3

Folic acid is found in green leafy vegetables, liver, yeast.
The word folate is related to folium which means leaf in
Latin.

Question 4

Functions of folic acid

Answer 4

• THF acts as a carrier of one carbon units.
• One carbon unit binds to THF through N5 or N10 or both N5 , N10 position. The THF coenzymes serve as acceptors or donors of one carbon units in a variety of reactions involved in amino acid and nucleic acid
  metabolism. Five of the major reactions in which THF
  is involved are given below:
  1. Conversion of serine to glycine: The conversion
  of serine to glycine is accompanied by the
  formation of N5 ,N10- methylene THF.
  2. Synthesis of thymidylate (pyrimidine nucleotide): The enzyme thymidylate synthase that converts deoxyuridylate (dUMP) into thymidylate (TMP) uses N5, N10-methylene THF as the methyl donor for this reaction. Thus, folate coenzyme plays a central role in the biosynthesis of nucleic acids.
  3. Catabolism of histidine : Histidine in the courseof its catabolism is converted into formiminoglutamate (FIGLU). This molecule can donate the formimino group to THF to produce N-5 formimino THF. In case of folic acid deficiency, FIGLU accumulates and is excreted in urine.
  4. Synthesis of purine: N5-Formyl THF intermediate formed in histidine catabolism is usedin the biosynthesis of purine and therefore in the formation of both DNA and RNA.
  5. Synthesis of methionine from homocysteine: Homocysteine is converted to methionine inpresence of N5-methyl THF, and vitamin B12. In this reaction the methyl group bound to cobalamin (Vitamin B12) is transferred to homocysteine to form methionine and the cobalamin then removes the methyl group from N5 -methyl THF to form THF.
  This step is essential for the liberation of free
  THF and for its repeated use in one carbon
  metabolism. In B12 deficiency, conversion of N5-methyl THF to free THF is blocked.

Question 5

Nutritional Requirements of folic acid

Answer 5

• The RDA of folate is 200 μg.
• Requirements increase during pregnancy and lactation.

Question 6

Deficiency Manifestations of folic acid

Answer 6

Folate deficiency frequently occurs particularly in pregnant women and in alcoholics. Clinical symptoms of folic acid deficiency include:
* Megaloblastic or macrocytic anemia:
The deficiency of folic acid leads to impairement of
synthesis of DNA. Impaired DNA synthesis, impairs
the maturation of erythrocytes. Consequently, megaloblasts are formed instead of normoblast. These megaloblasts are accumulated in the bone marrow and leads to megaloblastic anemia.
* Accumulation and excretion of FIGLU in the urine:
Folate deficiency blocks the last step of histidine
catabolism, due to lack of THF. This results in
accumulation of FIGLU in body, which leads to
increased excretion of FIGLU in urine.
* Hyperhomocysteinemia:
Due to folic acid deficiency the methylation of
homocysteine to methionine is impaired which leads to hyperhomocysteinemia. Increased level of homocystein is a risk factor for cardiovascular disease.
* Neural tube defect in fetus:
Since, folate is required for the formation of neural tube in early stage of gestation, the folate deficiency during early stage of pregnancy increases the risk of neural tube defect.

Question 7

Therapeutic Uses of folic acid

Answer 7

N5-methyl THF called folinic acid or citrovorum factor is used as therapeutic drug to overcome the folate deficiency.