BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 8. VITAMINS

8.3. Water-soluble vitamins

8.3.3. Folic acid

Chemical Structure and physicochemical properties. Folic acid, or vitamin Bc, consists of three structural fragments: a pteridine derivative, Para-aminobenzoic Acid, and one or more glutamic acid residues (Fig. 8.14). It was discovered as a substance that cures tropical macrocytic anemia, a growth factor for chicks (Bc) and the bacterium Lactobacillus casei, and was isolated from spinach leaves (Latin folium - leaf).

The reduction product of folic acid (FA), tetrahydrofolic acid (THFA, THF), is a component of Enzymes that carry out The transfer of single-carbon fragments. The reduction of the vitamin occurs in two stages: the first one, leading to The formation of dihydrofolic acid (DHFA), is catalyzed by folate reductase, and the second one by Dihydrofolate Reductase.

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Fig. 8.14. Folic (A) and tetrahydrofolic (B) acids

Both enzymes contain NADP as a coenzyme and are targets for anticancer drugs such as aminopterin and methotrexate.

Biochemical Functions. The reduced form of folic acid acts as a carrier for all single-carbon residues except the carboxyl group. The Donors of single-carbon groups transferred by THFA are most commonly the Amino Acids Serine, Glycine, and Histidine.

THFA transfers 6 groups:

Formyl -CHO; methyl -CH3, methylene -CH2-, methenyl -CH=, hydroxymethyl -CH₂OH, formimino -CH=NH. The attachment of these groups occurs through their covalent bonding to the 5th and (or) 10th nitrogen atom in the THFA molecule. Thus, N¹⁰-formyl-THFA, N⁵, N¹⁰-methylene-THFA, N⁵-methyl-THFA, etc., are formed. Such THFA derivatives are involved in the METABOLISM of amino acids such as Methionine and serine, as well as in the Synthesis of purine NUCLEOTIDES and The conversion of dUMP to dTMP.

Requirement and natural occurrence. The first sign of vitamin deficiency is impaired erythropoiesis (macrocytic anemia), as well as leukopenia and growth retardation. Folate hypovitaminosis leads to impaired regeneration of the epithelium, particularly in the gastrointestinal tract, because the synthesis of nucleotides required for DNA in actively dividing Cells is inhibited.

Dietary sources of the vitamin include fresh vegetables such as parsley, spinach, lettuce, and cauliflower, as well as Yeast, Liver, and Kidneys. It should be noted that boiling food destroys up to 95 % of the vitamin. Unlike humans and animals, microorganisms are capable of synthesizing folic acid de novo. Therefore, Microbial growth is inhibited by sulfonamides, which act as Competitive Inhibitors blocking the incorporation of para-aminobenzoic acid into The Biosynthesis of folic acid. The daily requirement is up to 200 mcg. The gut microbiota of humans and animals can also synthesize this vitamin. In medical practice, synthetic antagonists of folic acid are used as antitumor agents that inhibit nucleic acid synthesis.