Functions of Folate and Vitamin B12 and NTD Etiology

Folate acts as the intermediary in the transfer of methyl groups for two important processes in metabolism, namely the methylation reactions and the synthesis of the nucleic acids DNA and RNA

(Figure 1). The folate cofactor, N5-methyltetra-hydrofolate, acts via the vitamin B12-dependent enzyme, methionine synthase, to remethylate homo-cysteine to produce methionine, which is converted to S-adenosylmethionine (SAM) via S-adenosyl-methionine synthase. SAM is the universal methyla-tor necessary for the synthesis of essential proteins, lipids such as myelin, and DNA. The folate cofactor also acts via methionine synthase to synthesize tetrahydrofolate, which, unlike N5-methyltetra-hydrofolate, can be polyglutamated and thereafter used to produce the nucleic acids DNA and RNA. Simple deficiency or metabolic impairment in the biochemical functions of either folate or vitamin B12 could, by interrupting DNA biosynthesis or methylation reactions, interfere with cell growth and function and tissue development during a period of very rapid cell proliferation of the fetal neural crest, thereby preventing normal closure of the neural tube.

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