Phenylethanolamine N-methyltransferase (PNMT) is an enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine (adrenaline).

Several features of the structure like this folding lip suggest that PNMT is a recent adaptation to the catecholamine synthesizing enzyme family, evolving later than COMT, but before other methyltransferases like GNMT.

[6] The active site binding region for the cofactor SAM contains a rich number of pi bonds from phenylalanine and tyrosine residues in the active site help to keep it in its binding pocket through pi stacking.

[7] In the absence of an inhibitor or ligand, a phosphate group is bound to the active site to stabilize this region.

When PNMT crystals are grown in non-reducing solutions, two disulfide bonds form between cysteines 48 and 139 on opposite chains.

[10] PNMT is also involved in the biosynthesis of N-methylated trace amines: it metabolizes phenethylamine into N-methylphenethylamine (a positional isomer of amphetamine), p-octopamine into synephrine, and p-tyramine into N-methyltyramine.

[16] In animals who have had their pituitary gland removed, the addition of glucocorticoids significantly lengthens the half life of PNMT enzymes.

[17] SAM not only acts as a cofactor for PNMT, but also helps to stabilize the enzyme and increase the half life by making it more resistant to being cut by trypsin protease.

Certain neural tracts, the retina,[18] and in both atria and ventricles in the hearts are now being elucidated as sites of PNMT expression.

This suggests a central role that PNMT and epinephrine play in the synthesis of ethanol and pentobarbital induced sedation and intoxication.