Clinical significance of folic acid during pregnancy
According to clinical guidelines, a pregnant patient is indicated to take folic acid during the first 12 weeks of gestation. The level of recommendation validity is 1a, which corresponds to the highest degree of evidence. The biochemical rationale for this prescription is related to the key role of vitamin B9 in the synthesis of nucleic acids, without which the division of rapidly proliferating embryonic cells is impossible.
Structure and sources of vitamin B9
Folic acid, or vitamin B9, enters the body with food: meat, liver, kidneys, yeast, leafy greens. Part of the vitamin is synthesized by the intestinal microflora, but this amount is usually insufficient, so additional oral intake is necessary during pregnancy.
The structure of folic acid includes three components:
- pteridine ring;
- para-aminobenzoic acid (PABA);
- glutamic acid residue.
Knowledge of these constituent parts is necessary for understanding the mechanism of action of sulfonamides and for recognizing the structure in test questions.
Coenzyme form and transfer of one-carbon units
Like most vitamins, in the liver, folic acid is converted into its coenzyme form — tetrahydrofolic acid (H₄-folate, THF). The conversion consists in the addition of four hydrogen atoms to the vitamin molecule.
Main functions of THF:
- transfer of one-carbon units (—CH₃, —CH₂—, —CHO, etc.);
- participation in the synthesis of purine and pyrimidine bases;
- synthesis of glycine from serine;
- regeneration of methionine (via methyl-THF).
One-carbon units attach to two nitrogen atoms of the pteridine part of the molecule. Depending on the type of transferred group, derivatives are formed: methylene-THF, methyl-THF, formyl-THF, and others. These derivatives transfer the carbon unit to acceptor molecules during the assembly of nitrogenous bases.
Pathogenesis of deficiency: macrocytic anemia
With a deficiency of folic acid, the synthesis of purine and pyrimidine rings is disrupted, resulting in a decrease in the formation of nucleotides, the structural precursors of DNA and RNA. This critically affects rapidly dividing cells:
- erythrocyte precursors in the bone marrow;
- epithelium of mucous membranes;
- cells of the developing fetus in the first 12 weeks.
Erythroid cells cannot undergo mitosis due to a lack of DNA, but continue to grow in volume. Megaloblastic (macrocytic) anemia develops: erythrocytes become large, but few in number. In parallel, mucosal lesions, impaired wound healing, and fetal growth retardation occur — hence the mandatory prescription of vitamin B9 for pregnant women.
Sulfonamides: mechanism of selective action
Sulfonamides are antibacterial agents whose general structure is similar to that of para-aminobenzoic acid. This is a typical example of competitive inhibition based on the principle of a structural substrate analog.
Bacteria are not able to absorb finished folic acid from the outside and synthesize it independently from pteridine, PABA, and glutamate using their own enzymes (dihydropteroate synthase). A sulfonamide embeds into the active center of such an enzyme instead of PABA, blocking the assembly of the folate molecule. As a result, the bacterial cell is deprived of THF, cannot synthesize nucleotides, and stops dividing.
Human cells receive folic acid in ready-made form with food and do not have enzymes for its assembly. Therefore, sulfonamides do not exert a cytostatic effect on the tissues of the macroorganism — this is the selectivity of the antibacterial effect.
Key points
- Folic acid (vitamin B9) consists of pteridine, PABA, and glutamate; the coenzyme form is THF.
- THF transfers one-carbon units and ensures the synthesis of purines and pyrimidines.
- B9 deficiency leads to impaired DNA and RNA synthesis in rapidly dividing cells.
- Clinical manifestations of deficiency: macrocytic anemia, mucosal damage, fetal growth retardation.
- The prescription of folic acid in the first 12 weeks of pregnancy has a recommendation level of 1a.
- Sulfonamides are structural analogs of PABA, competitive inhibitors of folate synthesis in bacteria.
- The selectivity of sulfonamides is due to the fact that humans receive finished folic acid with food.
- THF is also involved in the synthesis of glycine from serine and the regeneration of methionine.