Physiology of Folate and Vitamin B₁₂in Health and Disease

Abstract

Folate is a water-soluble B-vitamin and enzymatic cofactor that is necessary for the synthesis of purine and thymidine nucleotides and for the synthesis of methionine from homocysteine. Impairment of folate-mediated one-carbon metabolic pathways can result from B-vitamin deficiencies and/or single nucleotide polymorphisms, and increases risk for pathologies, including cancer and cardiovascular disease, and developmental anomalies including neural tube defects. Although several well validated metabolic and genomic biomarkers for folate deficiency exist, our understanding of the biochemical and genetic mechanisms whereby impaired folate metabolism increases risk for developmental anomalies and disease is limited, as are the mechanisms whereby elevated folate intake protects against these pathologies. Therefore, current initiatives to increase folate intakes in human populations to ameliorate developmental anomalies and prevent disease, while effective, lack predictive value with respect to unintended adverse outcomes.

Folate, vitamin B6 and vitamin B12 in adolescence: serum concentrations, prevalence of inadequate intakes and sources in food

“…As vitaminas do complexo B têm merecido destaque como nutrientes-chave envolvidos na manutenção da saú-de e na prevenção de doenças 1 . O folato e as vitaminas metabolicamente relacionadas, dentre elas B6 e B12, têm sido associados à proteção contra alguns tipos de câncer e à redução da concentração sanguínea de homocisteína 2 .…”

Neural tube defects and folate: case far from closed

“…These onecarbon units are covalently bound to folate (R′ in FIG . 2) and are present over the whole range of oxidized and reduced forms of the one-carbon moiety, including the formyl and methyl derivatives (for reviews, see REFS [42][43][44] ). These one-carbon units are donated to THF by the amino acids histidine and serine, and glycine and its derivatives dimethylglycine and methylglycine (sarcosine), or by formate, and are used in the synthesis of DNA building blocks -that is, purines (adenine and guanine) and thymine (the thymidine precursor dTMP is shown in FIG.…”

“…Addition of a one-carbon unit and subsequent reduction steps produce 5-methyltetrahydrofolate (5-MeTHF) monoglutamate, which is taken up into the bloodstream and is the main form of folate in the circulation. From the blood, specific carriers or receptors transport 5-MeTHF into cells 42,43 (FIG. 3).…”

Cellular folate status modulates the expression of BCRP and MRP multidrug transporters in cancer cell lines from different origins

“…Folates play a key role in one-carbon metabolism, acting as coenzymes in many important reactions including the synthesis of DNA and RNA precursors, synthesis of several amino acids, and DNA methylation (7). Folate homeostasis is regulated by several enzymes in the folate metabolic pathway and also different transporters that mediate the uptake and efflux of folates from cells (8).…”