Folate: metabolism, biochemistry and role in disease processes.

Folate is a water-soluble B-vitamin that holds a key position in cell growth and development. By DNA synthesis and mitosis, as well as DNA methylation and regulation of gene expression, folate is deeply involved in cell life. Different chemical forms of folate are distinguishable by their oxidation state and specific type of one-carbon substitution. Folates occur in natural food as reduced methylated or formylated tetrahydrofolate. Several mechanisms act in concert to regulate the metabolic folate pathways and to ensure that all biological functions are fulfilled properly. A role for this B-vitamin in maintaining good health is confirmed by its implication in several types of pathological conditions such as cancer, cardiovascular disease, dementia, mental disorders, Down's syndrome, and serious conditions affecting pregnancy outcome. Other B-vitamins, such as methionine, betaine, choline, are involved in one-carbon metabolism. Inadequate enzyme activities and imbalances of substrates and cofactors in one-carbon metabolism may cause homocysteine and S-adenosylhomocysteine accumulation responsible for specific pathologic conditions. The folate pathway represents a powerful target for combating rapidly dividing cell processes such as those involved in cancer, bacteria and inflammation disorders. Numerous experimental studies traced different molecular pathways and tried to link folate depletion with DNA instability, mutagenesis, clone expansion, and/or anomalous DNA methylation. Biological and epidemiological evidences suggest that tetrahydrofolates account for proper DNA biosynthesis and support the hypothesis that insufficient folate supply may favour the development of cancer. How folate and/or other Bvitamins deficiencies influence carcinogenesis remains to be established.