Specific reactions involving single-carbon transfer by folic acid compounds are: (1) purine and pyrimidine synthesis, (2) interconversion of serine and glycine, (3) glycine-carbon as a source of C1 units for many syntheses, (4) histidine degradation, and (5) synthesis of methyl groups for such compounds as methionine, choline and thymine. Futhermore, folic acid is a vitamin from the B complex involved as a co-factor of thymidilate synthetase, which is an essential enzyme for DNA and RNA synthesis (Davis and Nicol, 1988).
Purine bases (adenine and guanine), as well as thymine (a pyrimidine base), are constituents of nucleic acids, and with a folic acid deficiency, there is a reduction in the biosynthesis of nucleic acids essential for cell formation and function. Hence, deficiency of the vitamin leads to impaired cell division and alterations of protein synthesis; these effects are most noticeable in rapidly growing tissues such as red blood cells, leukocytes, intestinal mucosa, embryos and fetuses. In absence of adequate nucleoproteins, normal maturation of primordial red blood cells does not take place and hematopoiesis is inhibited at the megaloblast stage. As a result of this megaloblastic arrest of normal red blood cell maturation in bone marrow, a typical peripheral blood picture results and is characterized by macrocytic anemia. White blood cell formation is also affected, resulting in thrombopenia leukopenia and old, multi-lobed neutrophils. Because of the relationship of folic acid to neural tube defects, the U.S. Public Health Service has recommended that pregnant women consume at least 0.4 mg of folic acid daily to reduce the risk of spina bifida or other neural tube defects developing in their pregnancy (Anonymous, 1996).
Vitamin B12 is necessary in reduction of one-carbon compounds of the oxidation stage of formate and formaldehyde, and in this way it participates with folic acid in biosynthesis of labile methyl groups. Folic acid is also essentially involved in all these reactions of labile methyl groups. The metabolism of labile methyl groups plays an important role in the biosynthesis of methionine from homocysteine and of choline from ethanolamine. Folic acid has a sparing effect on requirements of choline. The critical role of both folic acid and vitamin B12 on synthesis of choline is discussed in the choline section.
Additionally, folic acid has been reported to help maintain the immune system. The immune system was severely inhibited by folic acid deficiency in rats (Kumar and Axelrod, 1978), which is probably mediated through a reduction in DNA synthesis, resulting in impaired nuclear division. Grieshop et al. (1998) reported that gestational folic acid supplementation in sow diets enhanced the secondary postnatal immune response of the piglets to sheep red blood cell challenge.