Drug Metabolism Letters

Zhiyang Zhao
Cambridge, MA


Human Liver Enzymes Responsible for Metabolic Elimination of Tyramine, a Vasopressor Agent from Daily Food

Author(s): Toshiro Niwa, Norie Murayama, Hiromi Umeyama, Makiko Shimizu, Hiroshi Yamazaki.


Dietary tyramine is associated with hypertensive crises because of its ability to induce the release of catecholamines. The roles of monoamine oxidase (MAO), flavin-containing monooxygenase (FMO), and cytochrome P450 2D6 (CYP2D6) were studied in terms of the enzymatic elimination of tyramine in vitro at a substrate concentration of 1.0 μM, which is relevant to in vivo serum concentrations. Tyramine elimination by human liver supernatant fractions was decreased by ∼70% in the absence of NADPH. Pargyline, an MAO inhibitor, decreased tyramine elimination rates by ∼30%. Among recombinant P450 and FMO enzymes, CYP2D6 had a high activity in terms of tyramine elimination. Tyramine elimination rates were inhibited by quinidine and significantly correlated with bufuralol 1-hydroxylation activities (a CYP2D6 marker). Liver microsomes genotyped for CYP2D6*10/*10 and CYP2D6*4/*4 showed low and undetectable activities, respectively, compared with the wild-type CYP2D6*1/*1. The present results suggest that tyramine is eliminated mainly by polymorphic CYP2D6. Tyramine toxicity resulting from differences in individual metabolic elimination is thus genetically determined.

Keywords: Dopamine, CYP2D6, FMO3, MAO, liver, human, p-hydroxyphenyl acetic acid, incubation, centrifugation, Pargyline

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

Year: 2011
Page: [216 - 219]
Pages: 4
DOI: 10.2174/187231211796905026
Price: $58