Vitamin B9

Общее описание

Vitamin B₉ is now known officially as folic acid or folate, which is preferred because it is shorter. The term folic acid is derived from the Latin word folium meaning “leaf” and was coined by Mitchell et al. in 1941 to refer to a substance isolated from spinach leaves that was an essential growth factor in Streptococcus lactis R (now classified as Enterococcus hirae).
The chemical structure of folic acid was found to be composed of a pteridine heterocyclic system (rings A and B), p-aminobenzoic acid (PABA) and Glu; hence the name pteroylglutamate (PteGlu). In plants and bacteria, folic acid is synthesized by converting guanosine triphosphate (GTP) through a multistep sequence into the pteridine heterocycle. This is followed by dihydropteroate synthase (EC 2.5.1.15), which adds the PABA moiety and finally the glutamate residue is added by dihydrofolate synthase (EC 6.3.2.12). It is of note that the antibacterial sulfonamides compete with PABA for the bacterial form of dihydropteroate synthase and, thereby, interfere with bacterial folic acid synthesis. This results in a selective antibacterial effect because susceptible bacteria cannot utilize preformed folate from the environment.
Currently, folate (the preferred term) specifically refers to pteroylglutamate and folic acid refers to pteroylglutamic acid. Folate can also be used generically to refer to any of the members of the group of pteroylglutamates, their mixtures, differing one-carbon substituents, level of reduction, or number of glutamate residues.

Клиническое использование

Folic acid is used in the treatment of known or suspected folate deficiency or increased need as occurs during pregnancy. The most likely cause of folate deficiency in developed countries is alcoholism. Folic acid has also been shown to reduce homocysteine levels, which is a risk factor for cardiovascular disease independent of other risk factors.
However, although there is some evidence that folic acid supplementation may reduce the risk of stroke,the risk of other cardiovascular disease has not been proven to be affected. Some studies suggest that multivitamin preparations with folic acid taken prior to, and during pregnancy, may protect against congenital heart defects. Folate may also decrease the risk of colorectal cancer; however, once colorectal cancer develops it may act as a promoting agent.
One of the biologically active forms of folic acid, leucovorin (5-formyl-H4PteGlu), is used in the treatment of accidental overdoses of DHFR inhibitors, such as methotrexate, because it does not require bioactivation by DHFR as does folic acid. Leucovorin is also used concomitantly with, or shortly following, methotrexate, trimetrexate, pyrimethamine, trimethoprim, and related drug therapy to decrease the toxicity in sensitive cells.