Folic Acid (Folate): Functions

THF is involved in the following 1-carbon unit metabolic pathways:

  • Methylation of homocysteine to methionine – 5-methyl THF provides the necessary methyl groups, which are transferred to homocysteine by methylene THF reductase as well as methionine synthase – with vitamin B12 as cofactor – formation of THF and methionine.
  • Conversion of glycine to serine and serine to glycine, respectively – the conversion of amino acids occurs by transfer and acceptance of hydroxymethl groups with the help of tetrahydrofolic acid.
  • Histidine metabolism
  • Choline biosynthesis – choline is formed under the influence of THF from the amino acids lysine and methionine by methylation; as a component of lecithin (phosphatylcholine) and phosphatides, choline plays an essential role in phospholipid metabolism – choline participates, for example, in the construction of membranes.
  • Purine synthesis (formation of DNA and RNA) – in the synthesis of adenine and guanine (organic purine bases of DNA and RNA), THF is involved in the introduction of carbon atoms C2 and C8 into the purine ring.
  • Pyrimidine synthesis (formation of DNA and RNA) – THF is required for the synthesis of the two pyrimidine bases cytosine and thymine.

Homocysteine methyl transferase reaction

In the homocysteine methyl transferase reaction, the methyl group of 5-methyltetrahydrofolic acid is transferred to homocysteine to form the amino acid methionine and the metabolically active tetrahydrofolic acid. For this irreversible metabolic step, 5-methyl-THF as a methyl group donor provides the necessary methyl groups, which are transferred to homocysteine by the enzymes methylene-THF reductase and methionine synthase. Methionine synthase, which is necessary for the synthesis of methionine, requires vitamin B12 (in the form of methylcobalamin) as a cofactor. Methionine, which is formed by methylation of homocysteine, is one of the essential amino acids and, as S-adenosylmethionine (SAM), which is formed by reaction of methionine with ATP, is involved in a large number of metabolic processes.S-adenosylmethionine is a precursor in cysteine biosynthesis. It also plays an important role in methyl group transfer as a key compound. S-adenosylmethionine provides a methyl group for certain methylation reactions, such as ethanolamine to choline, norepinephrine to epinephrine, or phosphatidylethanolamine to lecithin. Furthermore, as the most important methyl group donor, the essential amino acid influences the biosynthesis of creatine, L-carnitine, nucleic acids and histidine, taurine and the antioxidant amino acid glutathione. SAM-dependent methylations always produce homocysteine as an intermediate product, which must be remethylated with the help of 5-methyl-THF and vitamin B12 (in the form of methylcobalamin) as a coenzyme.Without 5-methyl-THF and vitamin B12, the remethylation of homocysteine to methionine and tetrahydrofolic acid cannot occur. Finally, there is an interdependence between folate and vitamin B12 metabolism – synergy between vitamin B12 and folic acid.Vitamin B12 deficiency leads to blockage of the homocysteine methyl transferase reaction due to the absence of the B vitamin as a cofactor of methionine synthase in the transfer of the methyl group to homocysteine (methyl tetrahydrolate trap). As a result of the inhibition of the reaction, there is an increase in homocysteine levels (a risk factor for vascular diseases – homocysteine increases oxidative stress in blood vessels) on the one hand, and depletion of the organism of reactive folate compounds on the other. In addition, due to the inactive enzymes (methionine synthase and methylene THF reductase) responsible for the transfer of the methyl group to homocysteine, unregenerated methyl tetrahydrofolic acid accumulates, significantly increasing the serum folic acid concentration.As a result of the insufficient formation of metabolically active THF, the synthesis of storable folate polyglutamate compounds is prevented. This in turn results in impaired intracellular folate storage. Finally, vitamin B12 deficiency leads to low folate concentrations in all tissue cells including erythrocytes (red blood cells) in favor of folic acid levels in serum.

The importance of folic acid during periods of growth and development

Due to the essential function of vitamin B9 to be involved as a coenzyme form in DNA and RNA synthesis as well as protein metabolism, folate or folic acid is essential for adequate cell growth, normal cell division as well as optimal cell differentiation. The supply of vitamin B9 is particularly important during pregnancy. The increased folate requirement is based both on the significantly accelerated cell proliferation due to the enlargement of the uterus (womb), development of the placenta (placenta) and breast tissue, and increase in blood volume, and on the growth of the fetus (cell growth and differentiation).

Noncoenzymatic functions

In addition to the function of tetrahydrofolic acid to participate in protein and nucleic acid metabolism in the form of a coenzyme, THF can also influence certain metabolic reactions in a non-coenzymatic form. Accordingly, vitamin B9 is a component