Fig. (6) Schematic illustration showing the relationship between methylation cycle and folate metabolism. Folate metabolism is necessary for DNA biosynthesis and is required for remethylation process. SAM, a methyl group donor in transmethylation reactions, is produced from dietary methionine and participates in the remethylation of homocysteine in a vitamin B12-dependent reaction using the folate-dependent one-carbon pool as a methyl group source (5-methyl-THF). SAM/SAH is an index of transmethylation potential. SAM acts as an allosteric inhibitor of methylene-THF reductase (MTHFR), the enzyme catalyzed the irreversible reduction of 5, 10-methylene-THF to 5-methyl-THF. In turn, 5-methyl-THF is an inhibitor of GNMT, a key protein involved in the regulation of transmethylation by controlling the SAM/SAH ratio. THF= tetrahydrofolate, GNMT=N-methyltransferase, SAM= S-adenosyl methione, SAH=S-adenosyl homocysteine, MS= Methionie synthase (Vitamin B12), MTF= Methyltransferase.