Specific reactions involving single-carbon transfer by folic acid compounds are (a) purine and pyrimidine synthesis, (b) interconversion of serine and glycine, (c) glycine–carbon as a source of C1 units for many syntheses, (d) histidine degradation and (e) synthesis of methyl groups for such compounds as methionine, choline and thymine (a pyrimidine base).
Purine bases (adenine and guanine), as well as thymine, 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 for normal red blood cell maturation in bone marrow, a characteristic macrocytic anemia develops. White blood cell formation is also affected, resulting in thrombopenia, leukopenia and multi-lobed neutrophils.
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 (Savage and Lindenbaum, 1995). 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 in synthesis of choline is discussed in the choline chapter.
Folic acid is needed to maintain the immune system; the blastogenic response of T lymphocytes to certain mitogens is decreased in folic acid-deficient humans and animals, and the thymus is preferentially altered (Dhur et al., 1991). The effects of folic acid deficiency upon humoral immunity have been more thoroughly investigated in animals than in humans, and the antibody responses to several antigens have been shown to decrease. As de novo synthesis of methyl groups requires the participation of folic acid coenzymes, the effect of folic acid deficiency on pancreatic exocrine function was examined in rats (Balaghi and Wagner, 1992; Balaghi et al., 1993). Pancreatic secretion was significantly reduced in the deficient group compared with the pair-fed control groups after five weeks.