Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data

Abstract

Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use in determining the role of Epi in the central nervous system. Here we demonstrate that a routinely used assay for screening PNMT inhibitors is not appropriate for those inhibitors having K i values less than 1 μM. A revised assay has been developed that shows some inhibitors bind two orders of magnitude more tightly than previously reported.