Abstract
Reduced tetrahydrofolates (THF) are a family of cofactors that carry and chemically active one-carbons for the synthesis of purine nucleotides, thymidylate (dTMP), and methionine. Disruptions in one-carbon metabolism are associated with impaired DNA synthesis, increased uracil in DNA, elevated homocysteine, and various adverse physiological outcomes including neural tube defects and increased cancer risk. The cofactor 5-methyltetrahydrofolate (5-methylTHF) is used by the enzyme methionine synthase to convert homocysteine to methionine. 5-methyltetrahydrofolate can also be irreversibly oxidized to form the compound 4-hydroxy-5-methylTHF (Mefox), which is present in plasma and urine but its potential function(s) in human cells has not been ellucidated. In this study, the biological effects of Mefox were investigated in human cell lines by exploring its binding partners, effects on one-carbon metabolism and cell growth and proliferation. Mefox altered cell viability and caspase 3/7 activity (a marker of apoptosis), suggesting that Mefox may have specific cellular functions.
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