Norepinephrine N-methyltransferase in brain

Abstract

Norepinephrine N-methyltransferase (NMT, EC 2.1.1.28), the terminal enzyme in epinephrine biosynthesis, catalyzes the transfer of the labile methyl group from S-adenosyl-L-methionine (SAMe) to norepinephrine. The richest source of NMT is the adrenal medulla, quantitatively the most important site of epinephrine production in mammalian species. This enzyme is also present in brain in discrete neurons that apparently make and use epinephrine as their neurotransmitter substance (Hokfelt et al, 1974). Since NMT is the only enzyme unique to epinephrine biosynthesis, it has become a focus of study in recent years for those interested in epinephrine-forming neurons and their functions in brain. Inhibitors of NMT would reduce neurotransmitter synthesis in epinephrine-forming neurons in brain without directly affecting other neurons that use dopamine or norepinephrine as their transmitter. Thus NMT inhibitors are potentially useful tools for pharmacologic modification of the epinephrine-forming neurons in brain.