Enzymes of methylation metabolism

Enzymes of methylation metabolism, primarily methyltransferases, catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to diverse substrates including DNA, histones, proteins, RNA, and small molecules, enabling critical epigenetic modifications and post-translational regulation. These enzymes are classified into structural types such as class I (Rossmann fold SAM-binding), class II (SET domain for histone methylation), class III (membrane-associated), and radical SAM variants, with functions spanning gene expression control via DNA and histone methylation, neurotransmitter metabolism (e.g., via COMT, PNMT, HNMT), and detoxification processes. Dysregulation contributes to diseases like cancer through aberrant epigenetics, cardiovascular issues via homocysteine buildup, and neurological/mood disorders from impaired neurotransmitter synthesis. The one-carbon metabolism cycle, involving methionine synthase and folate pathways, recycles homocysteine to sustain SAM production, highlighting nutritional dependencies on methionine and folate. While individual methyltransferases (e.g., DNMT1/3 for DNA) serve as therapeutic targets, the broad category lacks specific drugs but poses challenges like off-target epigenetic effects and toxicity from metabolic intermediates.

Other names

MethyltransferasesMethylation enzymesProtein methyltransferasesDNA methyltransferasesHistone methyltransferasesSAM-dependent methyltransferases