Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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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.

Abstract:

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

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Article Details

VOLUME: 5
ISSUE: 3
Year: 2011
Page: [216 - 219]
Pages: 4
DOI: 10.2174/187231211796905026
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