Folic acid (the anion form is called folate) is a B-complex vitamin (once called vitamin M) that is important in preventing neural tube defects (NTDs) in the developing human fetus.
Folic acic and pregnancy
Since the discover of the link between insufficient folic acid and NTDs, governments and health organisations worldwide have made recommendations concerning folic acid supplementation for women intending to become pregnant. For example, the US Public Health service (see the URL given at page foot) recommends an extra 0.4mg/day, which can be taken as a pill. However, many researchers believe that supplementation in this way can never work effectively enough since not all pregnancies are planned and not all women will comply with the recommendation.
This has led to the introduction in many countries of fortification, where folic acid is added to flour with the intention of everyone benefiting from the associated raise in blood folate levels. This is not uncontroversial, with issues having been raised concerning individual liberty, and the masking effect of folate fortification on B12 deficiency or pernicious anaemia. However, most North and South American countries now fortify their flour, along with some of Europe and Israel. The UK has recently decided not to fortify, mainly because of the B12 concern.
Folic acid and ischaemic heart disease
Recent research also points out a further benefit of folic acid: that it can help combat high levels of homocysteine, and thus reduce the risk of ischaemic heart disease (IHD).
Biochemisty
In the form of a series of tetrahydrofolate compounds, folate derivatives are coenzymes in a number of single carbon transfer reactions biochemically, and also is involved in the synthesis of dTMP (2'-deoxythymidine-5'-phosphate) from dUMP (2'-deoxyuridine-5'-phosphate).
The pathway in the formation of tetrahydrofolate (FH4) is the reduction of folate (F) to dihydrofolate (FH2) by folate reductase, and then the subsequent reduction of dihydrofolate to tetrahydrofolate (FH4) by dihydrofolate reductase.
Methylene tetrahydrofolate (CH2=FH4) is formed from tetrahydrofolate by the addition of methylene groups from one of three carbon donors: formaldehyde, serine, or glycine. Methyl tetrahydrofolate (CH3-FH4) can be made from methylene tetrahydrofolate by reduction of the methylene, and methylidine tetrahydrofolate (CHO-FH4) is made by oxidation of the methylene tetrahydrofolate.
In other words:
F → FH2 → FH4 → CH2=FH4 → 1-carbon chemistry
A number of drugs interfere with the biosynthesis of folic acid and tetrahydrofolate. Among them are the antibiotics trimethoprim (which acts on dihydrofolate reductase), the sulfonamides (competitive inhibitors of para-aminobenzoic acid in the reactions of dihydropteroate synthetase), the antimalarial pyrimethamine, and the anticancer drug methotrexate (inhibits both folate reductase and dihydrofolate reductase).