Abstract
Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential one-carbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.
Highlights
The discovery of folic acid is the result of hard work of Lucy Wills, a medical researcher graduating from Cambridge University with the degree of botanist and geologist
There is direct evidence that folates might be absorbed across the colon via reduced folate carrier and proton-coupled folate transporter
Homologic models of reduced folate carrier and proton-coupled folate transporter were developed based on the data coming from the studies of bacterial transporters GlpT and LacY [17]
Summary
The discovery of folic acid is the result of hard work of Lucy Wills, a medical researcher graduating from Cambridge University with the degree of botanist and geologist. The core of the molecule consists of heterocyclic pterin structure, with a methyl group in the sixth position bound to para-aminobenzoic and glutamic acids so that folic acid presents pteroylglutamic acid (Figure 1). “Folates” is a generic term encompassing folic acid and its derivatives-dihydro-, tetrahydro-, methyl-, formyl-compounds possessing metabolic activity. Pterins derivates were first discovered as the pigments of butterfly wing (Greek πτερóν is translated as «a wing»). They are found in mammals, bacteria, blue-green algae, trypanosomes, plant chloroplasts acting as cofactors, intracellular signaling molecules, ultraviolet protectors, and fluorescent pigments [4]. Molibdopterins are essential for function of bacterial sulfite oxidase, nitrate reductase, dimethylsulfoxide reductase, nutritional C1-carbon chains, and metabolism of aromatic amino acids [2,3]. Researchers suggest that folic acid is involved in the elimination of divalent cations from the body [8]
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