Methylation

During conjugation with nucleophilic substrates, the methyl group attached to the sulfonium ion of SAM is transferred to the substrate forming the conjugate. SAM, having lost the methyl moiety, is converted to S-adenosylhomocysteine (SAH). SAH can be hydrolyzed to form adenosine and homocysteine. Homocysteine can either be converted to glutathione or methylated to form methionine, thus forming the starting point for SAM synthesis and completing the cycle.

Fuctional groups attacked are phenols, catechols, aliphatic and aromatic amines and sulfhydryl-containing groups. The enzymes that catalyze the transfer of the methyl group to these functional groups are the methyltransferases (MT). MTs are small, cytosolic, monomeric enzymes that utilize SAM as a methyl donor. There are many MTs but the best studied ones are named on the basis of their prototypical substrates: COMT (catechol O-methyltransferase), TPMT (thiopurine methyltransferase), TMT (thiol methyltransferase), HNMT (histamine N-methyltransferase) and NNMT (nicotinamide N-methyltransferase). An example of each enzyme mentioned is given. In each case, a typical substrate for the enzyme is shown.