SAMdependent

SAM-dependent is an adjective used to describe enzymes and biochemical reactions that require S-adenosyl-L-methionine (SAM) as a cofactor or substrate. The term is most commonly applied to methyltransferases, where SAM serves as the methyl donor, enabling the transfer of a methyl group to substrates such as DNA, RNA, proteins, or small molecules. In addition to methylation, SAM can participate in radical-based chemistry in radical SAM enzymes, which generate radical intermediates to drive diverse transformations.

Two broad families are typically grouped under SAM-dependent chemistry: classical AdoMet-dependent methyltransferases (MTases) and radical SAM enzymes. MTases often possess conserved sequence motifs and structural folds and produce S-adenosyl-L-homocysteine (SAH) after methyl transfer; SAH is a strong feedback inhibitor. These enzymes modify nucleic acids, histones, lipids, and small molecules, influencing gene regulation, metabolism, and signal transduction. Radical SAM enzymes use SAM to generate radicals, enabling reactions such as methylthiolation, complex cofactor biosynthesis, and RNA modifications; they commonly harbor iron-sulfur clusters and require reducing equivalents.

Biological significance. The availability of SAM and the activity of SAM-dependent enzymes link cellular methylation potential to nutrition and metabolism. Dysregulation of SAM-dependent methylation pathways is associated with cancer, neurological disorders, and metabolic diseases. Experimental study relies on measuring SAM/SAH ratios, enzyme assays, and structural analyses to understand substrate specificity and catalytic mechanisms.