Remethylated

Remethylated describes a state in which a molecule has received a methyl group (–CH3) as part of a chemical or biological process, often restoring a prior methylated form after demethylation or forming an expected methylated derivative. The term appears in biochemistry, molecular biology, and organic synthesis.

In biology, remethylation is a key step in one-carbon metabolism. It refers to the conversion of homocysteine back to methionine, a reaction that replenishes the essential methyl donor S-adenosylmethionine (SAM). This remethylation can proceed via methionine synthase, which uses 5-methyltetrahydrofolate as the methyl donor with vitamin B12 as a cofactor, or via betaine-homocysteine methyltransferase (BHMT), which uses betaine and is prominent in liver and kidney. Proper remethylation maintains methionine levels and prevents excess homocysteine, linked to vascular and metabolic disorders.

In epigenetics, remethylation can describe the re-establishment of DNA methylation marks after demethylation events. DNA methyltransferases, particularly maintenance DNMT1 and de novo DNMT3 enzymes, reintroduce methyl groups to cytosine bases, helping preserve or reconfigure heritable methylation patterns that influence gene expression.

In chemical synthesis, remethylation denotes adding a methyl group to a substrate that previously lacked or lost methylation. This can involve various methyl donors and reagents, including enzymatic methyl transfer in biocatalysis or chemical methylating agents, depending on the substrate and context.

Clinical relevance: disruptions to remethylation pathways, such as deficiencies in methionine synthase or related folate-cycle enzymes, can raise homocysteine levels and impair methylation capacity. Management may include supplementation with folate, vitamin B12, and, in some cases, betaine or other methyl donors.