Essay on Folic Acid | Vitamins

In this article we will discuss about Folic Acid:- 1. Introduction to Folic Acid 2. Chemistry on Folic Acid 3. Absorption and Transport 4. Excretion 5. Folic Acid 6. Normal Level in Serum 7. Source 8. Physiological Functions 9. Antagonists 10. Importance 11. Deficiency Symptoms 12. Management 13. Toxic Effects.

Contents:

1. Introduction to Folic Acid
2. Chemistry on Folic Acid
3. Absorption and Transport of Folic Acid
4. Excretion of Folic Acid
5. Folic Acid in Tissues
6. Normal Level of Folic Acid in Serum
7. Source of Folic Acid
8. Physiological Functions of Folic Acid
9. Folic Acid Antagonists
10. Importance of Folic Acid
11. Deficiency Symptoms of Folic Acid
12. Management of Folic Acid
13. Toxic Effects of Folic Acid

---

1. Introduction to Folic Acid:

a. In 1934, Wills showed that tropical mac­rocytic anemia in human beings was cured by a vitamin present in autolysed yeast extract.

b. In 1947, Pifiner et al isolated folic acid in a crystalline form from liver.

2. Chemistry on Folic Acid:

a. Folic acid (folacin, pteroylglutamic acid) is a compound made up of the Pteridine nucleus, P-amino-benzoic acid and glutamic acid. There are at least three nu­tritionally important and chemically re­lated compounds which occur in natural products belong to the folic acid group. These three compounds only differ in the number of glutamic acid residues attached to the Pteridine-amino-benzoic acid com­plex. The chemical structure of folic acid is given (Fig. 15.19). Folic acid is syn­onymous with vitamin Bc.

b. Folinic acid (leucovorin, folinic acid-SF [synthetic factor] is the reduced form of folic acid with a formyl group on position 5 (N⁵-formyl-tetrahydrofolic acid).

c. Folic acid is soluble in water.

d. It is stable to heat at neutral pH.

e. Its activity is not lost if it is heated at 120°C for 30 minutes at neutral pH.

f. Riboflavin accelerates the photo-oxida­tion of folic acid.

3. Absorption and Transport of Folic Acid:

a. Absorption of folic acid takes place along the whole length of the mucosa of the small intestine.

b. Mono-glutamates are produced from poly-glutamates which is ingested within the intestinal mucosa and di-hydro-folates are further reduced to tetra-hydro-folates by folic acid reductases.

c. The tetra-hydrofolates are then converted to methyl-tetrahydrofolate which enters the portal blood to be transported to the liver.

d. The vitamin then appears in the systemic circulation to supply the tissue.

e. The vitamin is transported to the plasma as methyl-tetrahydrofolate bound to pro­tein. The folate level of plasma obtained from umbilical cord blood is about 3 times that of the maternal plasma.

4. Excretion of Folic Acid:

a. 20% of ingested folate that remains unabsorbed is excreted in the feces.

b. 2-5 µg of folic acid is excreted in the urine daily. This may be increased after an oral dose of folate if the tissues are saturated.

c. Some folates are also excreted in saliva, sweat and bile.

5. Folic Acid in Tissues:

a. Tissue folate is about 70 mg in the whole body.

b. About one-third (5-15 µg/g) is in the liver.

c. Folate is incorporated into the erythro­cytes during erythropoiesis.

6. Normal Level of Folic Acid in Serum:

3-25 µg/1 of serum in healthy subjects.

7. Source of Folic Acid:

8. Physiological Functions of Folic Acid:

Coenzyme Activities:

a. Folic acid as a coenzyme is involved in the transfer and utilization of the single carbon (C -1) moiety.

Before functioning as a C- 1 carrier, folic acid is first reduced to 7, 8-dihydrofolic acid (H₂ folate) and then to the tetra-hydro compound (H₄ folate) catalyzed by folic acid reductase which uses NADPH as hy­drogen donor.

The reactions are given below in Fig. 15.21:

The “one carbon” moiety may be formyl (-CHO), formate(H⁺COO^–), methyl (CH₃^–) or hydroxymethyl (-CH₂OH). These are metabolically interchangeable.

Folinic acid (formyl tetrahydrofolate, f⁵ – H⁴ folate) is involved in the formylation of glutamic acid during the metabolic deg­radation of histidine; otherwise, it is metabolically inert. But f¹⁰-H₄ folate is metabolically active.

However, f⁵ can be converted to f^5-10 by formyl tetrahydrofolic acid isomerase as:

F^5-10-H₄ folate is also converted to N⁵– methyl-tetrahydrofolic acid by an NAD- dependent reductase and this methyl group is then transferred to de-oxy-adenosyl —B₁₂ (cobamide coenzyme) to form me­thyl B₁₂ which is an important donor of methyl group in the formation of methio­nine from homocysteine.

The other sources of the one-carbon moi­ety are the methyl groups of methionine, choline (by way of betaine) and thymine. These methyl groups are oxidized to -CH₂OH groups and carried as such on f^5-10-H₄ folate. The beta carbon of serine contributes hydroxymethyl group to the formation of a single carbon moiety.

The single (formyl) carbon present on the tetrahydrofolic acids is utilized in the fol­lowing ways:

(i) As a source of carbons 2 and 8 in the purine nucleus.

(ii) As a source of the formyl group on N- formyl methionine-tRNA which ini­tiates synthesis of peptide chains on ribosomes in microorganisms.

(iii) As a source of the formyl carbon in the formation of the beta carbon of serine in conversion of glycine to serine.

(iv) In the synthesis of methyl groups for methylation of homocysteine to form methionine or methylation of uracil to form thymine and for the synthesis of choline by the way of methyl groups from methionine.

b. Since the folic acid coenzymes take part in the synthesis of purines and thymine (the methylated pyrimidine of DNA) they are fundamentally involved in growth and reproduction of cells.

c. Folic acid coenzymes are not only con­fined to the hematopoietic system but are also generalized throughout the body.

d. In the metabolism of histidine, there is a folic acid-dependent step at the point where formiminoglutamic acid (Figlu) is converted to glutamic acid.

9. Folic Acid Antagonists:

1. The competitive inhibitor aminopterin (4-amino folic acid) is the most potent folic acid inhibitor.

2. Another antagonist is amethopterine (4-amino-10-methyl folic acid).

3. In animals the inhibitory effect of amtnopterin cannot be reversed by folic acid but only by folinic acid.

10. Importance of Folic Acid:

a. They have got clinical application in the treatment of malignant disease and con­firmation of the action of folic acid in cell growth.

b. Aminopterine has been used in the treat­ment of leukemia, particularly in children. A remission is temporarily observed in some patients but after a time the leukemic cells acquire the power to overcome the effects of the antagonist.

11. Deficiency Symptoms of Folic Acid:

Folic acid deficiency can result from low di­etary intake, in intestinal malabsorption syndromes and during pregnancy. A similar deficiency can occur as a result of prolonged administration of anticonvulsant drugs (phenytoin sodium and primidone). Folic acid antagonists also cause defi­ciency of folic acid.

The deficiency gives rise to a megaloblastic anemia. The nuclei of the neutrophil polymorpho­nuclear leukocytes contain more than the normal number of lobes. Other deficiency manifestations include retardation of growth, weakness, infertil­ity, inadequate lactation in females and increased output of formiminoglutamic acid (FIGLU) in the urine after histidine loading.

12. Management of Folic Acid:

(a) In folic acid deficiency, treatment with a daily dose of 5 mg of folic acid by mouth is sufficient; 5 mg once a week is always adequate for maintenance therapy.

(b) Folic acid must never be given other than with vitamin B₁₂ in Addisonian pernicious anemia or other vitamin B₁₂ deficiency anemia’s because of the risk of aggravat­ing or precipitating neurological features of vitamin B₁₂ depletion.

(c) Megaloblastic change due to vitamin B₁₂ deficiency is very rare in pregnancy. There­fore, it is reasonable to give folic acid sup­plements (350 µg daily) to all pregnant women.

(d) When a drug methotrexate inhibits dihydrofolate reductase, it is better to employ folinic acid to overcome the meta­bolic block. Folinic acid may be given as tablets, 15 mg daily orally or as an injec­tion intravenously or intramuscularly at a dose of 3 mg per ml.

(e) Folinic acid mouthwashes are used to counteract the oral side-effects of folate antagonist drugs.

(f) Megaloblastic disorder caused by other cytotoxic drugs which inhibit DNA syn­thesis is not reversed by either vitamin B₁₂ or folic acid administration.

(g) Severe hemolytic crises require treatment by blood transfusion. Folic acid 5 mg daily orally is prescribed to support the in­creased erythropoiesis.

(h) Following splenectomy, resistance to some infections may be impaired and daily penicillin V, 250 mg 12 hourly, is pre­scribed for at least 5 years.

13. Toxic Effects of Folic Acid:

Renal injury has been observed in animals re­ceiving large doses (50 mg./kg. body wt.) of folic acid intravenously.

Excess intake of folic acid may hasten the de­velopment of the nerve damage found in B₁₂ defi­ciency.