Figure 10 Structure of the cofactor Sadenosyl Lmethionine 22 SAM generic reactions of O and Smethylation a and of Nmethylation b

Methyltransferases involved in xenobiotic metabolism include:

• the main enzyme responsible for O-methylation, namely catechol O-methyltransferase (EC; COMT), which is mainly cytosolic but also exists in membrane-bound form;

• various enzymes involved in N-methylation and characterized by different substrate specificities, e.g., nicotinamide N-methyltransferase (EC, histamine N-methyltransferase (EC, phenylethanolamine N-methyl-transferase (EC, and a nonspecific arylamine N-methyltransferase (EC; and

• enzymes catalyzing S-methylation, namely the membrane-bound thiol methyltransferase (EC and the cytosolic thiopurine methyltransferase (EC

This classification makes explicit the three types of functionalities undergoing biomethylation, namely hydroxy (phenolic), amino, and thiol groups.

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