Journal
MOLECULES
Volume 26, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/molecules26123731
Keywords
folic acid; folate transporters; antifolates; folate overload
Funding
- Ministry of Science and Higher Education of the Russian Federation [75-15-2020-913]
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Folates, with a pterine core structure, play essential roles as coenzymes in one-carbon pathways and are found in various organisms. Deficiencies in folates can lead to severe health issues, while excessive intake may have negative effects on embryonic development and pre-cancerous cell growth.
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.
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