ENZYMATIC N-METHYLATION OF PHENELZINE CATALYZED BY PHENYLETHANOLAMINE N-METHYLTRANSFERASE

1. Phenelzine has been found to be methylated by enzymes obtained from bovine adrenal and some rat tissues in the presence of S-adenosylmethionine (SAM) as methyl group donor. 2. The methylated product was chromatographically (TLC and HPLC) identical with chemically synthesized N-methylphenelzine. The structure of this methylated phenelzine has been confirmed by a GC-MS procedure. 3. The phenelzine methyltransferase in the bovine adrenal has a molecular weight and isoelectric point identical with that of bovine adrenal phenylethanolamine N-methyltransferase (PNMT). 4. Methylated phenelzine possesses much reduced inhibitory activity towards monoamine oxidase (MAO). It can, however, be deaminated by MAO to produce phenylacetaldehyde, and subsequently phenylacetic acid. 5. Other hydrazine compounds, such as hydralazine, have also been found to be methylated by the adrenal enzyme. 6. Our finding of enzymatic methylation of hydrazine compounds is novel, and it may play a role in the metabolism of hydrazine drugs.