Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data.
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 microM. A revised assay has been developed that shows some inhibitors bind two orders of magnitude more tightly than previously reported.
Wu
Qian
Q
College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA.
Criscione
Kevin R
KR
Grunewald
Gary L
GL
McLeish
Michael J
MJ
D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D010625:Phenylethanolamine N-Methyltransferase