Periconceptional Maternal Folic Acid Supplementation Mediate DNA Methyla- tion Affecting Off spring Health

Folate, VitB12, choline, betaine and methionine both participate in the one-carbon metabolism (FOCM). Under the action of FOCM cycle enzymes, above-mentioned micronutrients convert to essential substrates for the following reactions of metabolic pathways. We eat folate and use the enzyme dihydrofolate reductase (DHFR) to convert into tetrahydrofolate (THF), which is the active form that carries one-carbon groups in a variety of reactions. Subsequently, with the action of serine-hydroxymethyltransferase (SHMT) and 5,10-methylenetetrahydrofolate reductase (MTHFR), THF transforms into 5,10-methylenetetrahydrofolate and finally convert to 5-methyl-THF. MTHFR serves a key role in one-carbon metabolism by converting methylene-THF to 5-methyl-THF. However, 5-methyl-THF on the one side serves as a transporter of the one-carbon unit participating in the purine and pyrimidine synthesis, which offer indispensable single carbon unit for nucleic acid synthesis. On another side, in the methionine synthase reaction, a methyl group is removed from 5-methyl-THF, which functions as a substrate, and is sequentially transferred to the vitamin B-12 coenzyme before homocysteine, thus forming methionine, to take part in DNA methylation and the synthesis of protein or phospholipid. All of the above reactions have an impact on cell growth, proliferation and differentiation, which are vital for the health of individuals.

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Author: Liu Huanyu

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